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1.
Article En | MEDLINE | ID: mdl-38695260

Photothermal therapy (PTT) represents a groundbreaking approach to targeted disease treatment by harnessing the conversion of light into heat. The efficacy of PTT heavily relies on the capabilities of photothermal agents (PTAs). Among PTAs, those based on organic dyes exhibit notable characteristics such as adjustable light absorption wavelengths, high extinction coefficients, and high compatibility in biological systems. However, a challenge associated with organic dye-based PTAs lies in their efficiency in converting light into heat while maintaining stability. Manipulating dye aggregation is a key aspect in modulating non-radiative decay pathways, aiming to augment heat generation. This review delves into various strategies aimed at improving photothermal performance through constructing aggregation. These strategies including protecting dyes from photodegradation, inhibiting non-photothermal pathways, maintaining space within molecular aggregates, and introducing intermolecular photophysical processes. Overall, this review highlights the precision-driven assembly of organic dyes as a promising frontier in enhancing PTT-related applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.


Coloring Agents , Photothermal Therapy , Humans , Coloring Agents/chemistry , Animals , Mice , Neoplasms/therapy
2.
Int J Biol Sci ; 20(7): 2779-2789, 2024.
Article En | MEDLINE | ID: mdl-38725849

Selenium (Se) is an essential trace element for biological processes. Seleno-amino acids (Se-AAs), known as the organic forms of Se, and their metabolic reprogramming have been increasingly recognized to regulate antioxidant defense, enzyme activity, and tumorigenesis. Therefore, there is emerging interest in exploring the potential application of Se-AAs in antitumor therapy. In addition to playing a vital role in inhibiting tumor growth, accumulating evidence has revealed that Se-AA metabolism could reshape the tumor microenvironment (TME) and enhance immunotherapy responses. This review presents a comprehensive overview of the current progress in multifunctional Se-AAs for antitumor treatment, with a particular emphasis on elucidating the crosstalk between Se-AA metabolism and various cell types in the TME, including tumor cells, T cells, macrophages, and natural killer cells. Furthermore, novel applications integrating Se-AAs are also discussed alongside prospects to provide new insights into this emerging field.


Amino Acids , Immunotherapy , Neoplasms , Selenium , Tumor Microenvironment , Humans , Immunotherapy/methods , Amino Acids/metabolism , Selenium/therapeutic use , Neoplasms/metabolism , Neoplasms/therapy , Neoplasms/drug therapy , Neoplasms/immunology , Animals , Killer Cells, Natural/metabolism , Killer Cells, Natural/immunology
3.
Int J Biol Sci ; 20(7): 2607-2621, 2024.
Article En | MEDLINE | ID: mdl-38725856

Immunotherapy has shown great potential in cancer treatment. However, even with the intervention of techniques such as immune checkpoint inhibitor therapy, tumors can still achieve immune escape, leading to a low response rate. Abnormal glycosylation is a widely recognized hallmark of cancer. The development of a complex "glyco-code" on the surface of tumor cells can potentially influence the immune system's ability to monitor tumors and can impact the anti-tumor immune response. Therefore, abnormal glycosylation has emerged as a promising target for immunotherapy. Many recent studies have shown that targeted glycosylation can reshape the tumor microenvironment (TME) and promote the immune response, thereby improving the response to immunotherapy. This review summarizes how glycosylation affects anti-tumor immune function in the TME and synthesizes the latest research progress on targeted glycosylation in immunotherapy. It is hoped that by elucidating the basic laws and biological connotations of glycosylation, this review will enable researcher to thoroughly analyze the mechanism of its influence on the immune metabolic regulation network, which will provide a theoretical tool for promoting the clinical application of glycosylation codes.


Immunotherapy , Neoplasms , Tumor Microenvironment , Glycosylation , Humans , Immunotherapy/methods , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/metabolism , Tumor Microenvironment/immunology , Animals
4.
Front Immunol ; 15: 1380065, 2024.
Article En | MEDLINE | ID: mdl-38726005

Introduction: Solid cancers Myeloid cells are prevalent in solid cancers, but they frequently exhibit an anti-inflammatory pro-tumor phenotype that contribute to the immunosuppressive tumor microenvironment (TME), which hinders the effectiveness of cancer immunotherapies. Myeloid cells' natural ability of tumor trafficking makes engineered myeloid cell therapy an intriguing approach to tackle the challenges posed by solid cancers, including tumor infiltration, tumor cell heterogenicity and the immunosuppressive TME. One such engineering approach is to target the checkpoint molecule PD-L1, which is often upregulated by solid cancers to evade immune responses. Method: Here we devised an adoptive cell therapy strategy based on myeloid cells expressing a Chimeric Antigen Receptor (CAR)-like immune receptor (CARIR). The extracellular domain of CARIR is derived from the natural inhibitory receptor PD-1, while the intracellular domain(s) are derived from CD40 and/or CD3ζ. To assess the efficacy of CARIR-engineered myeloid cells, we conducted proof-of-principle experiments using co-culture and flow cytometry-based phagocytosis assays in vitro. Additionally, we employed a fully immune-competent syngeneic tumor mouse model to evaluate the strategy's effectiveness in vivo. Result: Co-culturing CARIR-expressing human monocytic THP-1 cells with PD-L1 expressing target cells lead to upregulation of the costimulatory molecule CD86 along with expression of proinflammatory cytokines TNF-1α and IL-1ß. Moreover, CARIR expression significantly enhanced phagocytosis of multiple PD-L1 expressing cancer cell lines in vitro. Similar outcomes were observed with CARIR-expressing human primary macrophages. In experiments conducted in syngeneic BALB/c mice bearing 4T1 mammary tumors, infusing murine myeloid cells that express a murine version of CARIR significantly slowed tumor growth and prolonged survival. Conclusion: Taken together, these results demonstrate that adoptive transfer of PD-1 CARIR-engineered myeloid cells represents a promising strategy for treating PD-L1 positive solid cancers.


B7-H1 Antigen , Immunotherapy, Adoptive , Myeloid Cells , Receptors, Chimeric Antigen , Tumor Microenvironment , Animals , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , B7-H1 Antigen/immunology , Mice , Humans , Myeloid Cells/immunology , Myeloid Cells/metabolism , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/metabolism , Immunotherapy, Adoptive/methods , Tumor Microenvironment/immunology , Cell Line, Tumor , Female , Neoplasms/immunology , Neoplasms/therapy
5.
Front Immunol ; 15: 1384039, 2024.
Article En | MEDLINE | ID: mdl-38726000

Chimeric antigen receptor-natural killer (CAR-NK) cell therapy is a novel immunotherapy targeting cancer cells via the generation of chimeric antigen receptors on NK cells which recognize specific cancer antigens. CAR-NK cell therapy is gaining attention nowadays owing to the ability of CAR-NK cells to release potent cytotoxicity against cancer cells without side effects such as cytokine release syndrome (CRS), neurotoxicity and graft-versus-host disease (GvHD). CAR-NK cells do not require antigen priming, thus enabling them to be used as "off-the-shelf" therapy. Nonetheless, CAR-NK cell therapy still possesses several challenges in eliminating cancer cells which reside in hypoxic and immunosuppressive tumor microenvironment. Therefore, this review is envisioned to explore the current advancements and limitations of CAR-NK cell therapy as well as discuss strategies to overcome the challenges faced by CAR-NK cell therapy. This review also aims to dissect the current status of clinical trials on CAR-NK cells and future recommendations for improving the effectiveness and safety of CAR-NK cell therapy.


Immunotherapy, Adoptive , Killer Cells, Natural , Neoplasms , Receptors, Chimeric Antigen , Humans , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Killer Cells, Natural/immunology , Neoplasms/therapy , Neoplasms/immunology , Animals , Tumor Microenvironment/immunology , Clinical Trials as Topic , Antigens, Neoplasm/immunology
6.
PLoS One ; 19(5): e0303157, 2024.
Article En | MEDLINE | ID: mdl-38722943

STUDY OBJECTIVE: This study assessed the overall satisfaction with oncological care, including barriers to care, and identified its associated predictors among adult cancer patients in Vietnam. METHODS: In this cross-sectional study, we enrolled 300 adult cancer patients receiving inpatient care at a large urban oncological hospital between June and July 2022. Multivariable linear regression analyses examined associations between patient experiences and overall satisfaction ratings with cancer care. RESULTS: The mean overall satisfaction with oncological care was 8.82 out of 10, with 98.0% recommending this facility to their friends and family. In an adjusted model, being female (ß = 0.29, 95%CI: 0.04, 0.53), endorsing satisfaction with patient-nurse communication (ß = 0.33, 95%CI: 0.13, 0.53), patient-doctor communication (ß = 0.40, 95%CI: 0.11, 0.70), and psychoeducation about oncological medication management (ß = 0.30, 95%CI: 0.14, 0.45) were positively associated with overall ratings. In contrast, individuals with delays in treatment scheduling reported lower overall satisfaction with oncological care (ß = -0.38, 95%CI: -0.64, -0.13). Patients perceived health system, social/environmental, and individual barriers to care: worries about income loss due to attending treatment (43.3%); fear, depression, anxiety, and distress (36.8%); concerns about affordability of treatment (36.7%) and transportation problems (36.7%); and excessive waiting times for appointments (28.8%). CONCLUSION: This study showed high overall patient satisfaction with cancer care quality. Patient-centered communication strategies and psychoeducation about oncological medication management may be targeted to further enhance the cancer inpatient experience. Raising awareness about treatment options and services, and integrating mental health awareness into oncological care may ameliorate patient distress and facilitate greater satisfaction with oncological treatment processes.


Neoplasms , Patient Satisfaction , Humans , Female , Male , Vietnam , Middle Aged , Patient Satisfaction/statistics & numerical data , Neoplasms/therapy , Neoplasms/psychology , Adult , Cross-Sectional Studies , Aged , Cancer Care Facilities , Health Services Accessibility
7.
Cells ; 13(9)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38727261

Chimeric antigen receptor (CAR)-T cell therapy has proven to be a powerful treatment for hematological malignancies. The situation is very different in the case of solid tumors, for which no CAR-T-based therapy has yet been approved. There are many factors contributing to the absence of response in solid tumors to CAR-T cells, such as the immunosuppressive tumor microenvironment (TME), T cell exhaustion, or the lack of suitable antigen targets, which should have a stable and specific expression on tumor cells. Strategies being developed to improve CAR-T-based therapy for solid tumors include the use of new-generation CARs such as TRUCKs or bi-specific CARs, the combination of CAR therapy with chemo- or radiotherapy, the use of checkpoint inhibitors, and the use of oncolytic viruses. Furthermore, despite the scarcity of targets, a growing number of phase I/II clinical trials are exploring new solid-tumor-associated antigens. Most of these antigens are of a protein nature; however, there is a clear potential in identifying carbohydrate-type antigens associated with tumors, or carbohydrate and proteoglycan antigens that emerge because of aberrant glycosylations occurring in the context of tumor transformation.


Immunotherapy, Adoptive , Neoplasms , Receptors, Chimeric Antigen , Humans , Neoplasms/therapy , Neoplasms/immunology , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen/immunology , Tumor Microenvironment/immunology , Antigens, Neoplasm/immunology , T-Lymphocytes/immunology , Animals
8.
Psychooncology ; 33(5): e6348, 2024 May.
Article En | MEDLINE | ID: mdl-38730533

BACKGROUND: Pediatric cancer patients' oncology teams regularly take on a primary care role, but due to the urgent nature of cancer treatment, developmental screenings may be deprioritized. This leaves patients at risk of developmental diagnoses and referrals being delayed. AIMS: Clarify the current developmental surveillance and screening practices of one pediatric oncology team. MATERIALS AND METHODS: Researchers reviewed charts for patients (n = 66) seen at a pediatric oncology clinic in a suburban academic medical center to determine engagement in developmental screening (including functioning around related areas such as speech, neurocognition, etc.) and referrals for care in these areas. RESULTS: Developmental histories were collected from all patients through admission history and physical examination (H&P), but there was no routinized follow-up. Physicians did not conduct regular developmental screening per American Academy of Pediatrics guidelines for any patients but identified n = 3 patients with needs while the psychology team routinely surveilled all patients seen during this time (n = 41) and identified n = 18 patients as having delays. DISCUSSION: Physicians did not routinely screen for development needs beyond H&P and were inconsistent in developmental follow-up/referrals. Integrated psychologists were key in generating referrals for developmental-based care. However, many oncology patients were not seen by psychologists quickly or at all, creating a significant gap in care during a crucial developmental period. CONCLUSION: The case is made for further routinization of ongoing developmental screening in pediatric oncology care.


Developmental Disabilities , Neoplasms , Quality Improvement , Referral and Consultation , Humans , Child , Female , Male , Child, Preschool , Neoplasms/diagnosis , Neoplasms/therapy , Developmental Disabilities/diagnosis , Developmental Disabilities/therapy , Adolescent , Mass Screening , Pediatrics/standards , Medical Oncology , Infant , Primary Health Care
9.
Front Immunol ; 15: 1385190, 2024.
Article En | MEDLINE | ID: mdl-38711523

The discovery of Suppressor of Cytokine Signaling 1 (SOCS1) in 1997 marked a significant milestone in understanding the regulation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathways. Subsequent research deciphered its cellular functions, and recent insights into SOCS1 deficiencies in humans underscored its critical role in immune regulation. In humans, SOCS-haploinsufficiency (SOCS1-HI) presents a diverse clinical spectrum, encompassing autoimmune diseases, infection susceptibility, and cancer. Variability in disease manifestation, even within families sharing the same genetic variant, raises questions about clinical penetrance and the need for individualized treatments. Current therapeutic strategies include JAK inhibition, with promising results in controlling inflammation in SOCS1-HI patients. Hematopoietic stem cell transplantation and gene therapy emerge as promising avenues for curative treatments. The evolving landscape of SOCS1 research, emphasizes the need for a nuanced understanding of genetic variants and their functional consequences.


Signal Transduction , Suppressor of Cytokine Signaling 1 Protein , Humans , Suppressor of Cytokine Signaling 1 Protein/genetics , Suppressor of Cytokine Signaling 1 Protein/metabolism , Animals , Janus Kinases/metabolism , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , Neoplasms/genetics , Neoplasms/immunology , Neoplasms/therapy , Haploinsufficiency , STAT Transcription Factors/metabolism , STAT Transcription Factors/genetics , Genetic Therapy
10.
J Med Internet Res ; 26: e45719, 2024 May 08.
Article En | MEDLINE | ID: mdl-38718388

BACKGROUND: International health policies and researchers have emphasized the value of evaluating patient-reported outcomes (PROs) in clinical studies. However, the characteristics of PROs in adult tumor clinical trials in China remain insufficiently elucidated. OBJECTIVE: This study aims to assess the application and characteristics of PRO instruments as primary or secondary outcomes in adult randomized clinical trials related to tumors in China. METHODS: This cross-sectional study identified tumor-focused randomized clinical trials conducted in China between January 1, 2010, and June 30, 2022. The ClinicalTrials.gov database and the Chinese Clinical Trial Registry were selected as the databases. Trials were classified into four groups based on the use of PRO instruments: (1) trials listing PRO instruments as primary outcomes, (2) trials listing PRO instruments as secondary outcomes, (3) trials listing PRO instruments as coprimary outcomes, and (4) trials without any mention of PRO instruments. Pertinent data, including study phase, settings, geographic regions, centers, participant demographics (age and sex), funding sources, intervention types, target diseases, and the names of PRO instruments, were extracted from these trials. The target diseases involved in the trials were grouped according to the American Joint Committee on Cancer Staging Manual, 8th Edition. RESULTS: Among the 6445 trials examined, 2390 (37.08%) incorporated PRO instruments as part of their outcomes. Within this subset, 26.82% (641/2390) listed PRO instruments as primary outcomes, 52.72% (1260/2390) as secondary outcomes, and 20.46% (489/2390) as coprimary outcomes. Among the 2,155,306 participants included in these trials, PRO instruments were used to collect data from 613,648 (28.47%) patients as primary or secondary outcomes and from 74,287 (3.45%) patients as coprimary outcomes. The most common conditions explicitly using specified PRO instruments included thorax tumors (217/1280, 16.95%), breast tumors (176/1280, 13.75%), and lower gastrointestinal tract tumors (173/1280, 13.52%). Frequently used PRO instruments included the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30, the visual analog scale, the numeric rating scale, the Traditional Chinese Medicine Symptom Scale, and the Pittsburgh Sleep Quality Index. CONCLUSIONS: Over recent years, the incorporation of PROs has demonstrated an upward trajectory in adult randomized clinical trials on tumors in China. Nonetheless, the infrequent measurement of the patient's voice remains noteworthy. Disease-specific PRO instruments should be more effectively incorporated into various tumor disease categories in clinical trials, and there is room for improvement in the inclusion of PRO instruments as clinical trial end points.


Neoplasms , Patient Reported Outcome Measures , Humans , Cross-Sectional Studies , China , Neoplasms/therapy , Adult , Female , Male , Randomized Controlled Trials as Topic , Middle Aged , Clinical Trials as Topic
11.
Sci Rep ; 14(1): 10646, 2024 05 09.
Article En | MEDLINE | ID: mdl-38724530

Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe3O4 nanoclusters were developed for tumor-targeted dual-mode T1/T2-weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe3O4 nanoclusters synthesized by facilely modifying ultrasmall Fe3O4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe3O4 nanoclusters shows excellent dual-mode T1 and T2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe3O4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe3O4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.


Magnetic Resonance Imaging , Theranostic Nanomedicine , Magnetic Resonance Imaging/methods , Theranostic Nanomedicine/methods , Animals , Mice , Humans , Doxorubicin/chemistry , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Cell Line, Tumor , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neoplasms/therapy , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/therapeutic use , Succimer/chemistry , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology
12.
Nat Commun ; 15(1): 3933, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730243

As a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion. Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group. Also, higher levels of IL-18 in serum and tumor are detected with IMSA101 treatment. Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion.


Interleukin-18 , Membrane Proteins , Receptors, Chimeric Antigen , Animals , Interleukin-18/metabolism , Membrane Proteins/agonists , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mice , Receptors, Chimeric Antigen/metabolism , Receptors, Chimeric Antigen/immunology , Humans , Cell Line, Tumor , Mice, Inbred C57BL , T-Lymphocytes/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Lymphocyte Activation/drug effects , Immunotherapy, Adoptive/methods , Female , Neoplasms/immunology , Neoplasms/therapy , Neoplasms/drug therapy
13.
BMC Immunol ; 25(1): 29, 2024 May 11.
Article En | MEDLINE | ID: mdl-38730320

BACKGROUND: Several PD-1 antibodies approved as anti-cancer therapies work by blocking the interaction of PD-1 with its ligand PD-L1, thus restoring anti-cancer T cell activities. These PD-1 antibodies lack inter-species cross-reactivity, necessitating surrogate antibodies for preclinical studies, which may limit the predictability and translatability of the studies. RESULTS: To overcome this limitation, we have developed an inter-species cross-reactive PD-1 antibody, GNUV201, by utilizing an enhanced diversity mouse platform (SHINE MOUSE™). GNUV201 equally binds to human PD-1 and mouse PD-1, equally inhibits the binding of human PD-1/PD-L1 and mouse PD-1/PD-L1, and effectively suppresses tumor growth in syngeneic mouse models. The epitope of GNUV201 mapped to the "FG loop" of hPD-1, distinct from those of Keytruda® ("C'D loop") and Opdivo® (N-term). Notably, the structural feature where the protruding epitope loop fits into GNUV201's binding pocket supports the enhanced binding affinity due to slower dissociation (8.7 times slower than Keytruda®). Furthermore, GNUV201 shows a stronger binding affinity at pH 6.0 (5.6 times strong than at pH 7.4), which mimics the hypoxic and acidic tumor microenvironment (TME). This phenomenon is not observed with marketed antibodies (Keytruda®, Opdivo®), implying that GNUV201 achieves more selective binding to and better occupancy on PD-1 in the TME. CONCLUSIONS: In summary, GNUV201 exhibited enhanced affinity for PD-1 with slow dissociation and preferential binding in TME-mimicking low pH. Human/monkey/mouse inter-species cross-reactivity of GNUV201 could enable more predictable and translatable efficacy and toxicity preclinical studies. These results suggest that GNUV201 could be an ideal antibody candidate for anti-cancer drug development.


Cross Reactions , Immunotherapy , Programmed Cell Death 1 Receptor , Animals , Humans , Programmed Cell Death 1 Receptor/immunology , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Mice , Cross Reactions/immunology , Immunotherapy/methods , Hydrogen-Ion Concentration , Neoplasms/immunology , Neoplasms/therapy , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Cell Line, Tumor , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Epitopes/immunology , Antibodies, Monoclonal, Humanized/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Mice, Inbred C57BL , Female
14.
Mol Cancer ; 23(1): 98, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730483

The efficacy of Adoptive Cell Transfer Therapy (ACT) in combating hematological tumors has been well-documented, yet its application to solid tumors faces formidable hurdles, chief among them being the suboptimal therapeutic response and the immunosuppressive milieu within the tumor microenvironment (TME). Recently, Garcia, J. et al. present compelling findings shedding light on potential breakthroughs in this domain. Their investigation reveals the pronounced augmentation of anti-tumor activity in CAR T cells through the introduction of a T cell neoplasm fusion gene, CARD11-PIK3R3. The incorporation of this gene into engineered T cell therapy holds promise as a formidable tool in the arsenal of cancer immunotherapy. The innovative strategy outlined not only mitigates the requirement for high doses of CAR T cells but also enhances tumor control while exhibiting encouraging safety profiles. The exploration of the CARD11-PIK3R3 fusion gene represents an advancement in our approach to bolstering the anti-tumor efficacy of immunotherapeutic interventions. Nonetheless, the imperative for further inquiry to ascertain its transfection efficiency and long-term safety cannot be overstated. Nevertheless, this seminal investigation offers a beacon of hope in surmounting the formidable treatment impediments posed by solid tumors, paving the way for a transformative era in cancer therapeutics.


Immunotherapy, Adoptive , Neoplasms , Receptors, Chimeric Antigen , Humans , Neoplasms/therapy , Neoplasms/genetics , Neoplasms/immunology , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , Tumor Microenvironment/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Animals
15.
Int J Mol Sci ; 25(9)2024 Apr 25.
Article En | MEDLINE | ID: mdl-38731892

With the advent of immunotherapeutics, a new era in the combat against cancer has begun. Particularly promising are neo-epitope-targeted therapies as the expression of neo-antigens is tumor-specific. In turn, this allows the selective targeting and killing of cancer cells whilst healthy cells remain largely unaffected. So far, many advances have been made in the development of treatment options which are tailored to the individual neo-epitope repertoire. The next big step is the achievement of efficacious "off-the-shelf" immunotherapies. For this, shared neo-epitopes propose an optimal target. Given the tremendous potential, a thorough understanding of the underlying mechanisms which lead to the formation of neo-antigens is of fundamental importance. Here, we review the various processes which result in the formation of neo-epitopes. Broadly, the origin of neo-epitopes can be categorized into three groups: canonical, noncanonical, and viral neo-epitopes. For the canonical neo-antigens that arise in direct consequence of somatic mutations, we summarize past and recent findings. Beyond that, our main focus is put on the discussion of noncanonical and viral neo-epitopes as we believe that targeting those provides an encouraging perspective to shape the future of cancer immunotherapeutics.


Antigens, Neoplasm , Epitopes , Immunotherapy , Neoplasms , Humans , Antigens, Neoplasm/immunology , Antigens, Neoplasm/genetics , Neoplasms/immunology , Neoplasms/therapy , Neoplasms/genetics , Immunotherapy/methods , Epitopes/immunology , Epitopes/genetics , Exome/genetics , Mutation
16.
Int J Mol Sci ; 25(9)2024 Apr 25.
Article En | MEDLINE | ID: mdl-38731910

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment that utilizes viruses to preferentially infect and eliminate cancer cells while stimulating the immune response. In this review, we synthesize the current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy, focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated-signal sensing by neighboring cells, and the subsequent downstream activation of immune pathways. These sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how the molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting-cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.


Neoplasms , Oncolytic Virotherapy , Oncolytic Viruses , Humans , Oncolytic Virotherapy/methods , Neoplasms/therapy , Neoplasms/immunology , Oncolytic Viruses/genetics , Oncolytic Viruses/immunology , Animals , Signal Transduction , Immunity, Innate , Immunotherapy/methods
17.
Int J Oncol ; 64(6)2024 Jun.
Article En | MEDLINE | ID: mdl-38695252

Tumor­associated macrophages (TAMs) are essential components of the tumor microenvironment (TME) and display phenotypic heterogeneity and plasticity associated with the stimulation of bioactive molecules within the TME. TAMs predominantly exhibit tumor­promoting phenotypes involved in tumor progression, such as tumor angiogenesis, metastasis, immunosuppression and resistance to therapies. In addition, TAMs have the potential to regulate the cytotoxic elimination and phagocytosis of cancer cells and interact with other immune cells to engage in the innate and adaptive immune systems. In this context, targeting TAMs has been a popular area of research in cancer therapy, and a comprehensive understanding of the complex role of TAMs in tumor progression and exploration of macrophage­based therapeutic approaches are essential for future therapeutics against cancers. The present review provided a comprehensive and updated overview of the function of TAMs in tumor progression, summarized recent advances in TAM­targeting therapeutic strategies and discussed the obstacles and perspectives of TAM­targeting therapies for cancers.


Disease Progression , Neoplasms , Tumor Microenvironment , Tumor-Associated Macrophages , Humans , Tumor Microenvironment/immunology , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Neoplasms/immunology , Neoplasms/pathology , Neoplasms/therapy , Neoplasms/drug therapy , Neovascularization, Pathologic/immunology , Animals , Molecular Targeted Therapy/methods
18.
JMIR Mhealth Uhealth ; 12: e50620, 2024 May 01.
Article En | MEDLINE | ID: mdl-38717366

Background: Wearables that measure vital parameters can be potential tools for monitoring patients at home during cancer treatment. One type of wearable is a smart T-shirt with embedded sensors. Initially, smart T-shirts were designed to aid athletes in their performance analyses. Recently however, researchers have been investigating the use of smart T-shirts as supportive tools in health care. In general, the knowledge on the use of wearables for symptom monitoring during cancer treatment is limited, and consensus and awareness about compliance or adherence are lacking. objectives: The aim of this study was to evaluate adherence to and experiences with using a smart T-shirt for the home monitoring of biometric sensor data among adolescent and young adult patients undergoing cancer treatment during a 2-week period. Methods: This study was a prospective, single-cohort, mixed methods feasibility study. The inclusion criteria were patients aged 18 to 39 years and those who were receiving treatment at Copenhagen University Hospital - Rigshospitalet, Denmark. Consenting patients were asked to wear the Chronolife smart T-shirt for a period of 2 weeks. The smart T-shirt had multiple sensors and electrodes, which engendered the following six measurements: electrocardiogram (ECG) measurements, thoracic respiration, abdominal respiration, thoracic impedance, physical activity (steps), and skin temperature. The primary end point was adherence, which was defined as a wear time of >8 hours per day. The patient experience was investigated via individual, semistructured telephone interviews and a paper questionnaire. Results: A total of 10 patients were included. The number of days with wear times of >8 hours during the study period (14 d) varied from 0 to 6 (mean 2 d). Further, 3 patients had a mean wear time of >8 hours during each of their days with data registration. The number of days with any data registration ranged from 0 to 10 (mean 6.4 d). The thematic analysis of interviews pointed to the following three main themes: (1) the smart T-shirt is cool but does not fit patients with cancer, (2) the technology limits the use of the smart T-shirt, and (3) the monitoring of data increases the feeling of safety. Results from the questionnaire showed that the patients generally had confidence in the device. Conclusions: Although the primary end point was not reached, the patients' experiences with using the smart T-shirt resulted in the knowledge that patients acknowledged the need for new technologies that improve supportive cancer care. The patients were positive when asked to wear the smart T-shirt. However, technical and practical challenges in using the device resulted in low adherence. Although wearables might have potential for home monitoring, the present technology is immature for clinical use.


Feasibility Studies , Neoplasms , Wearable Electronic Devices , Humans , Adolescent , Male , Prospective Studies , Female , Neoplasms/psychology , Neoplasms/therapy , Adult , Wearable Electronic Devices/statistics & numerical data , Wearable Electronic Devices/standards , Wearable Electronic Devices/psychology , Cohort Studies , Denmark , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Young Adult
19.
Gut Microbes ; 16(1): 2341717, 2024.
Article En | MEDLINE | ID: mdl-38717360

The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, the impact of the gut microbiota on the initiation and progression of cancer is becoming increasingly evident, influencing the tumor microenvironment (TME) for both local and distant tumors. Moreover, it is even suggested to play a significant role in the process of tumor immunotherapy, contributing to high specificity in therapeutic outcomes and long-term effectiveness across various cancer types. Probiotics, with their generally positive influence on the gut microbiota, may serve as effective agents in synergizing cancer immunotherapy. They play a crucial role in activating the immune system to inhibit tumor growth. In summary, this comprehensive review aims to provide valuable insights into the dynamic interactions between probiotics, gut microbiota, and cancer. Furthermore, we highlight recent advances and mechanisms in using probiotics to improve the effectiveness of cancer immunotherapy. By understanding these complex relationships, we may unlock innovative approaches for cancer diagnosis and treatment while optimizing the effects of immunotherapy.


Gastrointestinal Microbiome , Immunotherapy , Neoplasms , Probiotics , Tumor Microenvironment , Probiotics/therapeutic use , Probiotics/administration & dosage , Probiotics/pharmacology , Humans , Immunotherapy/methods , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/microbiology , Tumor Microenvironment/immunology , Animals
20.
J Hematol Oncol ; 17(1): 33, 2024 May 14.
Article En | MEDLINE | ID: mdl-38745196

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence of the connections between the gut microbiota and cancer immunotherapy. Therefore, understanding the functional role of the gut microbiota in regulating immune responses to cancer immunotherapy is crucial for developing precision medicine. In this review, we extract insights from state-of-the-art research to decipher the complicated crosstalk among the gut microbiota, the systemic immune system, and immunotherapy in the context of cancer. Additionally, as the gut microbiota can account for immune-related adverse events, we discuss potential interventions to minimize these adverse effects and discuss the clinical application of five microbiota-targeted strategies that precisely increase the efficacy of cancer immunotherapy. Finally, as the gut microbiota holds promising potential as a target for precision cancer immunotherapeutics, we summarize current challenges and provide a general outlook on future directions in this field.


Gastrointestinal Microbiome , Immunotherapy , Neoplasms , Humans , Gastrointestinal Microbiome/immunology , Neoplasms/immunology , Neoplasms/therapy , Immunotherapy/methods , Animals
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