Tumour Immunotherapy and Applications of Immunological Products: A Review of Literature.

Malignant tumors, characterized by uncontrolled cell proliferation, are a leading global health challenge, responsible for over 9.7 million deaths in 2022, with new cases expected to rise to 35 million annually by 2050. Immunotherapy is preferred to other cancer therapies, offering precise targeting of malignant cells while simultaneously strengthening the immune system's complex responses. Advances in this novel field of science have been closely linked to a deeper knowledge of tumor biology, particularly the intricate interplay between tumor cells, the immune system, and the tumor microenvironment (TME), which are central to cancer progression and immune evasion. This review offers a comprehensive analysis of the molecular mechanisms that govern these interactions, emphasizing their critical role in the development of effective immunotherapeutic products. We critically evaluate the current immunotherapy approaches, including cancer vaccines, adoptive T cell therapies, and cytokine-based treatments, highlighting their efficacy and safety. We also explore the latest advancements in combination therapies, which synergistically integrate multiple immunotherapeutic strategies to overcome resistance and enhance therapeutic outcomes. This review offers key insights into the future of cancer immunotherapy with a focus on advancing more effective and personalized treatment strategies.

RNA modifications in cancer immune therapy: regulators of immune cells and immune checkpoints.

RNA modifications are epigenetic changes that alter the structure and function of RNA molecules, playing a crucial role in the onset, progression, and treatment of cancer. Immune checkpoint inhibitor (ICI) therapies, particularly PD-1 blockade and anti-CTLA-4 treatments, have changed the treatment landscape of virous cancers, showing great potential in the treatment of different cancer patients, but sensitivity to these therapies is limited to certain individuals. This review offers a comprehensive survey of the functions and therapeutic implications of the four principal RNA modifications, particularly highlighting the significance of m6A in the realms of immune cells in tumor and immunotherapy. This review starts by providing a foundational summary of the roles RNA modifications assume within the immune cell community, focusing on T cells, NK cells, macrophages, and dendritic cells. We then discuss how RNA modifications influence the intricate regulatory mechanisms governing immune checkpoint expression, modulation of ICI efficacy, and prediction of ICI treatment outcomes, and review drug therapies targeting genes regulated by RNA modifications. Finally, we explore the role of RNA modifications in gene editing, cancer vaccines, and adoptive T cell therapies, offering valuable insights into the use of RNA modifications in cancer immunotherapy.

The Laws of Attraction: Chemokines as Critical Mediators in Cancer Progression and Immunotherapy Response in Bladder Cancer.

Bladder cancer (BCa) is a prevalent urogenital malignancy, characterized by a myriad of genetic and environmental risk factors that drive its progression. Approximately 75% of bladder tumors are non-muscle-invasive at diagnosis. For such cases, bladder preservation is often feasible with intravesical chemotherapy or immunotherapy. However, the high recurrence rates associated with these tumors necessitate multiple cystoscopic examinations and biopsies, leading to significant financial burden and morbidity. Despite bladder tumors exhibiting one of the highest cancer mutational loads, which typically correlates with improved responses to immunotherapy, challenges persist. The tumor microenvironment serves as a nexus for interactions between tumor cells and the immune system, wherein chemokines and chemokine receptors orchestrate the recruitment of immune cells. This review addresses existing gaps in our understanding of chemokine dynamics in BCa by elucidating the specific roles of key chemokines in shaping the immune landscape of the tumor microenvironment (TME). We explore how dysregulation of chemokine signaling pathways contributes to the recruitment of immunosuppressive cell populations, such as Tregs and monocytes, leading to an unfavorable immune response. Additionally, we highlight the potential of these chemokines as predictive biomarkers for tumor progression and treatment outcomes, emphasizing their role in informing personalized immunotherapeutic strategies. By integrating insights into chemokine networks and their implications for immune cell dynamics, this review seeks to provide a comprehensive understanding of the interplay between chemokines and the immune microenvironment in BCa. Furthermore, we discuss the potential of targeting these chemokine pathways as innovative immunotherapeutic strategies, paving the way for enhanced treatment responses and improved patient outcomes.

Influence of the gut microbiota on immune cell interactions and cancer treatment.

The tumour microenvironment represents a novel frontier in oncological research. Over the past decade, accumulating evidence has underscored the importance of the tumour microenvironment (TME), including tumour cells, stromal cells, immune cells, and various secreted factors, which collectively influence tumour growth, invasion, and responses to therapeutic agents. Immune cells within the TME are now widely acknowledged to play pivotal roles in tumour development and treatment. While some perspectives have posited that immune cells within the TME facilitate tumour progression and confer resistance to therapeutic interventions, contrasting conclusions also exist. Affirmative and negative conclusions appear to be context dependent, and a unified consensus has yet to be reached. The burgeoning body of research on the relationship between the gut microbiota and tumours in recent years has led to a growing understanding. Most studies have indicated that specific components of the gut microbiota, such as unique bacterial communities or specific secretory factors, play diverse roles in regulating immune cells within the TME, thereby influencing the prognosis and outcomes of cancer treatments. A detailed understanding of these factors could provide novel insights into the TME and cancer therapy. In this study, we aimed to synthesise information on the interactions between the gut microbiota and immune cells within the TME, providing an in-depth exploration of the potential guiding implications for future cancer therapies.

Fruquintinib in refractory metastatic colorectal cancer: a multicenter real-world study.

BACKGROUND: Fruquintinib has been approved by the Food and Drug Administration for refractory metastatic colorectal cancer (mCRC). In clinical practice, fruquintinib is sometimes used in combination with other drugs, but its efficacy and safety are still unknown. In this study, we present a comprehensive analysis of the real-world treatment modalities involving fruquintinib in late-line settings for mCRC across six centers in China. PATIENTS AND METHODS: Patients with refractory mCRC who received fruquintinib treatment in six centers in China between 1 January 2021 and 31 June 2022 were included in this study. Patients were categorized into two cohorts: the monotherapy group (treated solely with fruquintinib) and the combined group (received fruquintinib combined with chemotherapy and/or anti-programmed cell death protein 1 antibodies). Demographic, clinical, survival, and safety data were retrospectively analyzed. The study was registered at clinicaltrials.gov as NCT06202417. RESULTS: A total of 520 patients were included in this study. The median follow-up time was 9.7 months. The disease control rate was 64.8%. The median progression-free survival was 5.0 months and the median overall survival was 11.4 months. Of them, 387 (74.4%) were treated with fruquintinib alone, while 133 (25.6%) were administered fruquintinib plus chemotherapy and/or anti-programmed cell death protein 1 antibodies, respectively. Adverse events were reported by 91.3% (457/520) of patients. The rate of grade 3 or 4 toxicity was 42.4% (237/520). No treatment-related death occurred. CONCLUSION: Fruquintinib, either as a standalone treatment or in combination with other medications, demonstrates substantial efficacy and favorable tolerability in refractory mCRC patients.

A systematic review of cardiovascular toxicities induced by cancer immune therapies: Underlying mechanisms, clinical manifestations and therapeutic approaches.

Immunotherapy has revolutionized the management of various types of cancers, even those previously deemed untreatable. Nonetheless, these medications have been associated with inflammation and damage across various organs. These challenges are exemplified by the adverse cardiovascular impacts of cancer immunotherapy, which need comprehensive understanding, clarification, and management integrated into the overall care of cancer patients. Numerous anticancer immunotherapies have been linked to the prevalence and severity of cardiovascular toxicity. These challenges emphasize the importance of conducting fundamental and applied research to elucidate disease causes, discover prognostic indicators, enhance diagnostic methods, and create successful therapies. Despite the acknowledged importance of T cells, there remains a knowledge gap regarding the inciting antigens, the reasons for their recognition, and the mechanisms of how they contribute to cardiac cell injury. In this review, we summarize the molecular mechanism, epidemiology, diagnosis, pathophysiology and corresponding treatment of cardiovascular toxicity induced by immunotherapy, including immune checkpoint inhibitors (ICIs), adoptive cell therapies (ACT), and bi-specific T-cell engagers (BiTEs) among others. By elucidating these aspects, we aim to provide a better understanding of immunotherapies in cancer treatment and offer guidance for their clinical application.

Supramolecular nanomedicine in the intelligent cancer therapy: recent advances and future.

In recent years, the incidence of cancer has been increasing year by year, and the burden of the disease and the economic burden caused by it has been worsening. Although chemotherapy, immunotherapy, targeted therapy and other therapeutic means continue to progress, they still inevitably have problems such as high toxicity and side effects, susceptibility to drug resistance, and high price. Photothermal therapy and photodynamic therapy have demonstrated considerable advantages in cancer imaging and treatment due to their minimally invasive and selective nature. However, their development has been constrained by challenges related to drug delivery. In recent times, drug delivery systems constructed based on supramolecular chemistry have been the subject of considerable interest, particularly in view of their compatibility with the high permeability and long retention effect of tumors. Furthermore, the advantage of dissociating the active ingredient under pH, light and other stimuli makes them unique in cancer therapy. This paper reviews the current status of supramolecular nanomedicines in cancer therapy, elucidating the challenges faced and providing a theoretical basis for the efficient and precise treatment of malignant tumors.

Exploring the Clinical Implications of RPL3 Presence in BRCA-Associated Cancers: Unraveling the Interplay With Cancer Immunity.

Background: Few studies have explored the expression profile of RPL3 in breast cancer (BRCA). Our research provided an in-depth analysis of RPL3 expression patterns in BRCA, highlighting its significance for therapy prediction and prognosis. Methods: RPL3 was notably elevated in malignant cells, and its expression level was closely associated with tumor size and overall survival outcomes. Our study also identified RPL3-related terms and pathways and revealed a strong correlation between RPL3 expression and breast carcinoma immunity, demonstrating inconsistent expression levels in various immune cell lines. In addition, we examined the relationship between RPL3 expression and tumor mutational burden (TMB) in BRCA. To assess the clinical implications of BRCA chemotherapy, we investigated the correlation between RPL3 expression levels and drug sensitivity. Results: Our findings suggest that RPL3 plays a critical role in the BRCA process and is associated with immune infiltration, indicating its potential as a novel immunotherapy target in BRCA treatment. Conclusions: In summary, our research underscores the importance of RPL3 expression levels in tumorigenesis and its potential for guiding BRCA immunotherapy.

Prognostic Impact of Bone Metastasis in Patients With Metastatic Urothelial Carcinoma Treated With Durvalumab With or Without Tremelimumab in the DANUBE Study.

INTRODUCTION: Bone metastases (BM) in metastatic urothelial carcinoma (mUC) may impact patient outcomes, but their independent effect with immune checkpoint inhibitors (ICIs) is uncertain. We aimed to assess the impact of BM and PD-L1 status on outcomes in mUC patients treated with ICIs. PATIENTS AND METHODS: This post hoc analysis of the DANUBE study included 1032 mUC patients treated with durvalumab (D), D + tremelimumab (T), or standard chemotherapy (SoC). Patients were categorized by BM status and assessed for median overall survival (mOS) and median progression-free survival (mPFS) stratified by PD-L1 expression and treatment arm.  RESULTS: Among all patients enrolled in the study, those with BM had a lower mOS than those with no BM (8.7 vs. 15.8 months; P < .0001). Patients with BM and high PD-L1 expression, treated with D or D + T, had numerically longer mOS than patients with BM and low PD-L1 expression. In contrast, in the chemotherapy arm, there was no difference in mOS for BM or no BM, based on PD-L1 expression. Patients with BM had shorter mPFS compared to no BM (2.6 vs. 5.4 months; P < .0001). The study is limited by its post hoc nature. CONCLUSION: Presence of BM was associated with worse outcomes across treatment arms. Patients with BM and high PD-L1 expression treated with D or D + T had longer mOS, suggesting potential benefits of ICIs in this subgroup. Consideration of BM and PD-L1 status in treatment decisions for mUC patients receiving ICIs may improve clinical outcomes.

Gas immnuo-nanomedicines fight cancers.

Certain gas molecules, including hydrogen (H2), nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), oxygen (O2) and sulfur dioxide (SO2) exhibit significant biological functionalities that can modulate the immune response. Strategies pertaining to gas-based immune therapy have garnered considerable attention in recent years. Nevertheless, delivering various gas molecules precisely into tumors, which leads to enhanced anti-tumor immunotherapeutic effect, is still a main challenge. The advent of gas treatment modality with desirable immunotherapeutic efficiency has been made possible by the rapid development of nanotechnology, which even derives the concept of the gas immnuo-nanomedicines (GINMs). In light of the fact, we herein aim to furnish a cutting-edge review on the latest progress of GINMs. The underlying mechanisms of action for several gases utilized in cancer immunotherapy are initially outlined. Additionally, it provides a succinct overview of the current clinical landscape of gas therapy, and introduces GINMs specifically designed for cancer treatment based on immunotherapeutic principles across multiple strategies. Last but not least, we address the challenges and opportunities associated with GINMs, exploring the potential future developments and clinical applications of this innovative approach.

A retrospective comparison of induction chemoimmunotherapy versus chemotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy in stage III non-small cell lung cancer.

Background: Patients with locally advanced non-small cell lung cancer (LA-NSCLC) usually bear high tumor burden and are not tolerated well to concurrent chemoradiation therapy (CRT) followed by consolidation immunotherapy. We investigated the feasibility of chemoimmunotherapy as induction therapy before CRT for LA-NSCLC. Methods: We retrospectively analyzed data from 91 patients with unresectable stage III NSCLC treated with either induction chemoimmunotherapy or chemotherapy before CRT. Tumor responses, survival statistics, and toxic effects were compared. The dosimetric parameters of the RT protocol were evaluated. The primary endpoint was progression-free survival (PFS). The overall response (ORR), the depth of response (DpR) were accessed at the end of CRT (ORRinduc+CRT, DpRinduc+CRT) and induction therapy (ORRinduc, DpRinduc). Results: The median PFS (mPFS) were significantly longer in the chemoimmunotherapy induction group (13.5 months vs. 11.2 months; HR, 0.56; 95% CI, 0.32-0.97; p=0.036). The ORRinduc+CRT, median DpRinduc+CRT (mDpRinduc+CRT) and mDpRinduc were significantly higher in the chemoimmunotherapy induction group (ORRinduc+CRT, 84.0% vs. 65.9%, p=0.044; mDpRinduc+CRT, 49.5% vs. 39.0%, p = 0.012; mDpRinduc, 38.5% vs. 28.0%, p=0.044). Incidence of treatment-related adverse events (AE) was similar between groups, with myelosuppression being the most common grade ≥ 3 AE. Regarding radiotherapy, adopting a mapping strategy with a 5-8 mm margin for clinical tumor volume resulted in decreased radiation doses to critical organs in the chemoimmunotherapy induction group. Conclusions: Chemoimmunotherapy induction therapy before CRT improves efficacy with comparable incidence of AEs compared to chemotherapy induction in LA-NSCLC patients. Further studies are warranted to validate these findings.

Tumor-Selective Nano-Dispatcher Enforced Cancer Immunotherapeutic Effects via Regulating Lactate Metabolism and Activating Toll-Like Receptors.

The development of tumors relies on lactate metabolic reprogramming to facilitate their unchecked growth and evade immune surveillance. This poses a significant challenge to the efficacy of antitumor immunity. To address this, a tumor-selective nano-dispatcher, PIMDQ/Syro-RNP, to enforce the immunotherapeutic effect through regulation of lactate metabolism and activation of toll-like receptors is developed. By using the tumor-targeting properties of c-RGD, the system can effectively deliver monocarboxylate transporters 4 (MCT4) inhibitor (Syro) to inhibit lactate efflux in tumor cells, leading to decreased lactate levels in the tumor microenvironment (TME) and increased accumulation within tumor cells. The reduction of lactate in TME will reduce the nutritional support for regulatory T cells (Tregs) and promote the effector function of T cells. The accumulation of lactate in tumor cells will lead to tumor death due to cellular acidosis. In addition, it will also reduce the uptake of glucose by tumor cells, reduce nutrient plunder, and further weaken the inhibition of T cell function. Furthermore, the pH-responsive release of Toll-like receptors (TLR) 7/8 agonist IMDQ within the TME activates dendritic cells (DCs) and promotes the infiltration of T cells. These findings offer a promising approach for enhancing tumor immune response through targeted metabolic interventions.

Multi-omics analysis reveals the landscape of tumor microenvironments in left-sided and right-sided colon cancer.

Background: Distinct clinical features and molecular characteristics of left-sided colon cancer (LCC) and right-sided colon cancer (RCC) suggest significant variations in their tumor microenvironments (TME). These differences can impact the efficacy of immunotherapy, making it essential to investigate and understand these disparities. Methods: We conducted a multi-omics analysis, including bulk RNA sequencing (bulk RNA-seq), single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing (WES), to investigate the constituents and characteristic differences of the tumor microenvironment (TME) in left-sided colon cancer (LCC) and right-sided colon cancer (RCC). Result: Deconvolution algorithms revealed significant differences in infiltrated immune cells between left-sided colon cancer (LCC) and right-sided colon cancer (RCC), including dendritic cells, neutrophils, natural killer (NK) cells, CD4 and CD8 T cells, and M1 macrophages (P < 0.05). Notably, whole-exome sequencing (WES) data analysis showed a significantly higher mutation frequency in RCC compared to LCC (82,187/162 versus 18,726/115, P < 0.01). Single-cell analysis identified predominant tumor cell subclusters in RCC characterized by heightened proliferative potential and increased expression of major histocompatibility complex class I molecules. However, the main CD8 + T cell subpopulations in RCC exhibited a highly differentiated state, marked by T cell exhaustion and recent activation, defined as tumor-specific cytotoxic T lymphocytes (CTLs). Immunofluorescence and flow cytometry results confirmed this trend. Additionally, intercellular communication analysis demonstrated a greater quantity and intensity of interactions between tumor-specific CTLs and tumor cells in RCC. Conclusion: RCC patients with an abundance of tumor-specific cytotoxic T lymphocytes (CTLs) and increased immunogenicity of tumor cells in the TME may be better candidates for immune checkpoint inhibitor therapy.

Oncolytic adenovirus encoding decorin and CD40 ligand inhibits tumor growth and liver metastasis via immune activation in murine colorectal tumor model.

Colorectal cancer (CRC) is the second common cause of cancer mortality worldwide, and it still lacks effective approaches for relapsed and metastatic CRC. Recently, oncolytic virus has been emerged as a promising immune therapeutic strategy. In this study, we develop a novel oncolytic adenovirus, rAd.mDCN.mCD40L, which drive oncolytic activity by telomerase reverse transcriptase promoter (TERTp). rAd.mDCN.mCD40L expressed both mouse genes of decorin (mDCN) and CD40 ligand (mCD40L), and produced effective cytotoxicity in both human and mouse CRC cells. Moreover, oncolytic adenovirus mediated mDCN over-expression inhibited Met expression in vitro. In CT26 subcutaneous tumor model, intratumorally delivery of oncolytic adenoviruses could inhibit tumor growth and liver metastasis, while mDCN and/or mCD40L armed oncolytic adenoviruses produced much more impressive responses. No obvious toxicity was detected in lung, liver and spleen. Moreover, mDCN and/or mCD40L armed oncolytic adenoviruses altered the immune state to activate anti-tumor responses, including increasing CD8+ T effector cells and CD4+ memory T cells, reducing MDSCs and Tregs in peripheral blood. Furthermore, mDCN and/or mCD40L armed oncolytic adenoviruses mediated mDCN and/or mCD40L expression in tumors, and up-regulated Th1 cytokines and reduced Th2 cytokines in tumors, which will be benefit for remodeling tumor microenvironment. Importantly, rAd.mDCN.mCD40L and rAd.mCD40L prevented tumor liver metastasis much more effectively than rAd.Null and rAd.mDCN. Therefore, rAd.mDCN.mCD40L and rAd.mCD40L are promising approaches for CRC therapy.

Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus. Despite the increasing utilization of immunostimulatory regimens in cancer, effects on the thymus and naïve T cell output have not been well characterized. Using both mouse and human systems, the thymic effects of systemic immunostimulatory regimens, such as high dose IL-2 (HD IL-2) with or without agonistic anti-CD40 mAbs and acute primary viral infection, were investigated. These regimens produced a marked acute thymic involution in mice, which correlated with elevated serum glucocorticoid levels and a diminishment of naïve T cells in the periphery. This effect was transient and followed with a rapid thymic "rebound" effect, in which an even greater quantity of thymocytes was observed compared to controls. Similar results were observed in humans, as patients receiving HD IL-2 treatment for cancer demonstrated significantly increased cortisol levels, accompanied by decreased peripheral blood naïve T cells and reduced T-cell receptor excision circles (TRECs), a marker indicative of recent thymic emigrants. Mice adrenalectomized prior to receiving immunotherapy or viral infection demonstrated protection from this glucocorticoid-mediated thymic involution, despite experiencing a substantially higher inflammatory cytokine response and increased immunopathology. Investigation into the effects of immunostimulation on middle aged (7-12 months) and advance aged (22-24 months) mice, which had already undergone significant thymic involution and had a diminished naïve T cell population in the periphery at baseline, revealed that even further involution was incurred. Thymic rebound hyperplasia, however, only occurred in young and middle-aged recipients, while advance aged not only lacked this rebound hyperplasia, but were entirely absent of any indication of thymic restoration. This coincided with prolonged deficits in naïve T cell numbers in advanced aged recipients, further skewing the already memory dominant T cell pool. These results demonstrate that, in both mice and humans, systemic immunostimulatory cancer therapies, as well as immune challenges like subacute viral infections, have the potential to induce profound, but transient, glucocorticoid-mediated thymic involution and substantially reduced thymic output, resulting in the reduction of peripheral naive T cells. This can then be followed by a marked rebound effect with naïve T cell restoration, events that were shown not to occur in advanced-aged mice.

Immune Characteristics and Immunotherapy of HIV-Associated Lymphoma.

In the era of antiretroviral therapy (ART), mortality among people living with the human immunodeficiency virus (HIV) has significantly decreased, yet the population of people living with HIV remains substantial. Among people living with HIV (PLWH), HIV-associated lymphoma (HAL) has surpassed Kaposi's sarcoma to become the most common tumor in this population in developed countries. However, there remains a dearth of comprehensive and systematic understanding regarding HIV-associated lymphomas. This review aims to shed light on the changes in the immune system among PLWH and the characteristics of the immune microenvironment in HIV-associated lymphoma, with a specific focus on the immune system's role in these individuals. Additionally, it seeks to explore recent advancements in immunotherapy for the treatment of HIV-associated lymphoma, intending to enhance strategies for immunotherapy in this specific population.

Specifically Editing Cancer Sialoglycans for Enhanced Immunotherapy In Vivo through Aptamer-Enzyme Chimeras.

Immune checkpoints blockade (ICB) therapies have demonstrated remarkable clinical success in treating cancer. However, its objective response rate remains suboptimal because current therapies rely on limited immune checkpoints that failed to cover the multiple immune evasion pathways of cancer. To explore potential ICB strategies, herein, we propose a glycoimmune checkpoint elimination (glycoICE) therapy depending on targeted edition of sialoglycans on tumor cell surface using aptamer-enzyme chimera (ApEC). The ApEC is readily generated via a one-step bioorthogonal procedure, allowing for large-scale and uniform production. The ApEC is able to target and desialylate cancer cells, leading to the elimination of sialoglycan-Siglec axis, which in turn activates immune cells and enhances immunotherapy efficiency. In addition to its remarkable therapeutic efficiency, the ApEC exhibits high tumor selectivity, which helps to avoid side effects caused by indiscriminate desialylation of normal tissues. Furthermore, the ApEC has the potential to be a versatile platform for specifical editing of sialoglycans in different tumor models by adjusting the aptamer sequences targeting associated with specific protein markers. This research not only introduces a novel molecular tool for the effective editing of sialoglycans in complex environments, but also provides valuable insights for advancing DNA-based drugs towards in vivo and clinical applications.

Non-nutritional use of human milk as a therapeutic agent in neonates: Brain, gut, and immunologic targets.

Human milk (HM) exposure improves short- and long-term outcomes for infants due to a complex milieu of bioactive, stem cell, anti-inflammatory, anti-microbial, and nutritive components. Given this remarkable biologic fluid, non-nutritional utilization of HM as a targeted therapeutic is being explored in pre-clinical and clinical studies. This article describes recent research pertinent to non-nutritional uses of HM for neurologic, gastrointestinal, and infectious pathologies in neonates, as well as future directions.

Combined Immune Therapy Proves Effective in an Advanced Hepatocellular Carcinoma Patient With Poor Liver Reserve: A Case Report.

There are no effective treatment options for patients with poor performance status and limited liver reserve, classified as Child-Pugh Grade B and C. A 61-year-old man with a prior medical history of hepatitis C virus infection was admitted to the hospital with abdominal distension and significant abdominal ascites. He was diagnosed with stage IVB hepatocellular carcinoma (HCC), characterized by multiple metastases to lymph nodes, lungs, and bones. After receiving combined immune therapy, including dendritic cell therapy targeting WT1 and α-Galactosylceramide, natural killer cells, and Nivolumab, the patient showed significant improvement in HCC and liver reserve function and followed standard treatment. Combined immune therapy is potentially an important option for patients with advanced hepatocellular carcinoma and poor liver reserve function, especially for relatively young patients.