Research progress of CAR-T immunotherapy in solid tumors combined with new strategies / 中国药科大学学报

@#In recent years, the chimeric antigen receptor T-cell (CAR-T) therapy has achieved breakthrough progress in the treatment of hematologic malignancies. However, when it comes to solid tumors, numerous challenges persist.These include limited CAR-T cell infiltration, susceptibility to T cell exhaustion, off-target effects, and more.Thus, novel therapeutic strategies are imperative to enhance the efficacy of CAR-T therapy for solid tumors. In comparison to standalone CAR-T approaches, the combination of CAR-T with other tumor treatment modalities has demonstrated remarkable effectiveness in both preclinical and clinical research.This review article summarizes the advancements in combining CAR-T with various solid tumor treatments: antibody drugs, oncolytic viruses, tumor vaccines, and nanomedicines.The objective is to furnish a theoretical foundation and novel perspectives for the development of innovative CAR-T combination strategies tailored for solid tumor therapy.

Progress of Chimeric Antigen Receptor Gene Modified-T Cell Immunotherapy for Thoracic Malignancies / 肿瘤防治研究

With a deepened understanding of the pathophysiology and pathogenesis of thoracic malignancies, the treatment has been transited from traditional treatment on the basis of surgery, radiotherapy, and chemotherapy to individualized and precise targeted therapy and immunotherapy. As an antitumor immunotherapy, chimeric antigen receptor gene-modified T (CAR-T) cells have been approved by the FDA for the treatment of hematological malignancies in five CAR-T products. They have also achieved good therapeutic effects in solid tumors. However, significant challenges remain in the clinical application of CAR-T cell immunotherapy in thoracic malignancies. In this review, the latest research progress of CAR-T cell immunotherapy in the treatment of thoracic malignancies were summarized, including the basic characteristics of CAR-T cells, the popular target antigens, and the existing problems and challenges, to provide new ideas and strategies for clinical immunotherapy of thoracic malignancies.

Dormancy and Survival Mechanism of Disseminated Tumor Cell and Its Role in Prevention and Treatment of Solid Tumor Metastasis / 肿瘤防治研究

The prevention and treatment of tumor metastasis can significantly improve the survival of patients with solid tumors. However, there is still a lack of effective drugs for the prevention and treatment of metastasis. The main reason is that the existing intervention and therapeutic drugs are difficult to achieve precise prevention and treatment of metastasis. Due to disseminated tumor cells (DTCs) already exist in the metastatic target organs of early postoperative patients, they are difficult to be detected with existing imaging techniques, and there is a lack of effective intervention drugs and efficacy evaluation systems. When DTCs grow to be detectable by imaging, the patient is already in the advanced stage of cancer, which has become a bottleneck restricting the breakthroughs in metastasis prevention and treatment. This paper reviews the dormancy and survival mechanism of DTCs in metastatic target organs and its intervention strategies, in order to promote the curative effect of metastasis prevention and treatment.

Clinical Characteristics and Prognosis of Patients with Hematological Malignancies Superimposed with Solid Tumors / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and prognosis of hematological malignancies superimposed patients with solid tumors.@*METHODS@#The clinical data of 30 patients with more than two kinds of malignancy (the second is hematological malignancy) from October 2011 to October 2020 in Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University were collected and analyzed retrospectively. The overall survival time was used as the prognostic evaluation standard, and the survival of patients were analyzed by KaplanMeier method. Logrank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 30 patients.@*RESULTS@#Among 30 cases, 20 were male, 10 were female, the median age of onset of the second tumor was 70 years old. The common types of the secondary hematological malignancies to solid tumors are myelodysplastic syndrome, acute myeloid leukemia, multiple myeloma. Univariate analysis showed that patients' gender, age, type of solid tumors, the onset of interval between two kinds of tumor, chromosome karyotype were not related to do with the patients' overall survival time. Type of hematologic disease, ECOG score were associated with patients' overall survival time, and the multivariate analysis showed that the type of hematologic disease and ECOG score were independent risk factors for patients with poor prognosis.@*CONCLUSION@#Patients superimposed with solid tumors complicated with myelodysplastic syndrome or acute leukemia and ECOG score ≥3 have poor prognosis and shorter overall survival time, which are independent risk factors influencing the prognosis. Bone marrow injury, immune dysfunction and genetic susceptibility after chemoradiotherapy may be the main causes of these diseases.

Advances in research of Musashi2 in solid tumors / 南方医科大学学报

RNA binding protein (RBP) plays a key role in gene regulation and participate in RNA translation, modification, splicing, transport and other important biological processes. Studies have shown that abnormal expression of RBP is associated with a variety of diseases. The Musashi (Msi) family of mammals is an evolutionarily conserved and powerful RBP, whose members Msi1 and Msi2 play important roles in the regulation of stem cell activity and tumor development. The Msi family members regulate a variety of biological processes by binding and regulating mRNA translation, stability and downstream cell signaling pathways, and among them, Msi2 is closely related to embryonic growth and development, maintenance of tumor stem cells and development of hematological tumors. Accumulating evidence has shown that Msi2 also plays a crucial role in the development of solid tumors, mainly by affecting the proliferation, invasion, metastasis and drug resistance of tumors, involving Wnt/β-catenin, TGF-β/SMAD3, Akt/mTOR, JAK/STAT, Numb and their related signaling pathways (Notch, p53, and Hedgehog pathway). Preclinical studies of Msi2 gene as a therapeutic target for tumor have achieved preliminary results. This review summarizes the molecular structure, physiological function, role of Msi2 in the development and progression of various solid tumors and the signaling pathways involved.

Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent / 中西医结合学报

OBJECTIVE@#The chemo-preventative and therapeutic properties of selenium nanoparticles (SeNPs) have been documented over recent decades and suggest the potential uses of SeNPs in medicine. Biogenic SeNPs have higher biocompatibility and stability than chemically synthesized nanoparticles, which enhances their medical applications, especially in the field of cancer therapy. This study evaluated the potential of green-synthetized SeNPs by using berberine (Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors (ESTs).@*METHODS@#SeNPs containing Ber (SeNPs-Ber) were synthesized using Ber and Na@*RESULTS@#Treatment with SeNPs-Ber significantly improved the survival rate and decreased the body weight and tumor size, compared to the EST group. SeNPs-Ber reduced oxidative stress in tumor tissue, as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glutathione levels. Moreover, SeNPs-Ber activated an apoptotic cascade in the tumor cells by downregulating the B-cell lymphoma 2 (Bcl-2) expression rate and upregulating the Bcl-2-associated X protein and caspase-3 expression rates. SeNPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue, compared to the EST group.@*CONCLUSION@#Our study provides a new insight into the potential role of green-synthesized SeNPs by using Ber as a promising anticancer agent, these molecules could be used alone or as supplementary medication during chemotherapy.

Collection of autologous peripheral hematopoietic stem cells in patients with sequential double transplantation of solid tumors and effect analysis / 中国输血杂志

【Objective】 To explore the methods and safety of autologous peripheral hematopoietic stem cells collection in patients with sequential double transplantation of solid tumors and conduct efficacy analysis. 【Methods】 Peripheral blood stem cells were collected from 27 patients with solid tumors after routine mobilization of rhG-CSF and rhGM-CSF.A specific program was made for the patients.The condition and cooperation degree of children were comprehensively evaluated before cell collection, and a femoral venous catheterization was inserted to ensure the cells collected smoothly.A mononuclear cell collection(MNC) program was selected, and machine parameters were set based on the patient's low body weight.The number of mononuclear cell (MNC) and the CD34+ cell was detected by flow cytometry for retrospective analysis. 【Results】 A total of 73 cell collections were performed in 27 patients, and the number of mononuclear cells and CD34+ cells was 12.586(10.22~19.586)×108/kg and 13.575(7.275~23.825)×106/kg, respectively, which can meet the requirement of sequential double transplantation. No intoxication of citrate and other serious adverse reactions occurred, and the follow-up was generally in good condition. 【Conclusion】 The method is effective and safe for pediatric patients, even for pediatric patients with low weight. Sufficient stem cells can be collected for patients with solid tumors by this method to meet the requirement of sequential double transplantation.

Advances in extracorporeal photopheresis / 中国输血杂志

Extracorporeal photopheresis(ECP) is a bidirectional cellular immunomodulatory therapy based on leukapheresis, which can mediate not only immunopotentiation but also immunosuppression. Clinically, ECP has been observed to have good efficacy in the treatment of cutaneous T cell lymphoma(CTCL), graft versus-host disease(GVHD) and solid organ transplant rejection, also the US Food and Drug Administration(FDA) has approved ECP for the treatment of CTCL. The treatment guidelines for GVHD in the US and Europe also include ECP, however, there is a lack of relevant guidelines in China. Although the exact mechanism of ECP is not fully explained, recent studies provide a theoretical basis for a further understanding of the bidirectional regulation of ECP.The initial hypothesis was the combination of 8-methoxypsoralen(8-MOP) and ultraviolet A(UVA) to induce apoptosis of immune cells. As the research progressed, this idea was transformed into the differentiation of monocyte to dendritic cell(DC), cytokine alteration and the regulatory T cell(Treg) stimulation.In this article, the current exploration of the immunomodulatory mechanism in ECP and its clinical application were reviewed, also the latest molecular mechanism of ECP mediated immunopotentiation and immunosuppression was comprehensively analyzed, meanwhile the further promotion and clinical application of ECP in China had been prospected.

Investigation of effect of paclitaxel on netrin 1 and factor 8 in Ehrlich solid tumors / Investigación del efecto del paclitaxel en netrina 1 y factor 8 en tumores sólidos de Ehrlich

SUMMARY: Cancer known as a malignant tumor, is a class of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The Ehrlich tumor is a mammary adenocarcinoma of mice developed in solid and ascitic forms. This study was aimed to investigate the effects of paclitaxel on Netrin 1 and Factor 8 expression and also in tumor cell proliferation, apoptosis, angiogenesis, and development of tumor in Ehrlich solid tumors treated with paclitaxel. In this study, 26 adult Balb/C male mice were used. 6 of them were used as stock. Ehrlich ascites cells taken from animals in stock were injected subcutaneously from the neck area to all animals. The mice were randomly assigned to two groups of ten rats per group. Paclitaxel treatment group 10 mg/kg were administered to mice intraperitoneally (i.p.) 4,9, and 14th days. 15th day the animals were sacrificed and tumor tissues were taken. Paraffin-embedded solid tumor sections were stained Hematoxylin & Eosin, Masson's Trichrome. Also solid tumor sections were stained immunohistochemically with Netrin1 and Factor 8. Tunel method was applied to determine apoptosis. Paclitaxel applied as a therapeutic Ehrlich solid tumor reduced the volume of tumors in the treatment groups. At the end of the experiments, in the treatment groups' significantly reduced the Netrin 1 expression and microvessel density compared to the group control. Also paclitaxel in the treatment group increased the number of apoptotic cells. We suggest that decreasing the expression of Netrin 1 would be reduced vessel density and increased apoptosis.

RESUMEN: El cáncer, conocido como tumor maligno, es una clase de enfermedad que involucra un crecimiento celular anormal con potencial de invadir o diseminarse a otras partes del cuerpo. El tumor de Ehrlich es un adenocarcinoma mamario de ratones desarrollado en formas sólidas y ascíticas. Este estudio tuvo como objetivo investigar los efectos del paclitaxel en la expresión de Netrin 1 y Factor 8 y también en la proliferación de células tumorales, apoptosis, angiogénesis y desarrollo de tumores sólidos de Ehrlich tratados con paclitaxel. En esta investigación se utilizaron 26 ratones machos Balb / C adultos. Seis de ellos se utilizaron como stock. Se inyectaron por vía subcutánea células de ascitis de Ehrlich tomadas de animales en la zona del cuello. Los ratones se asignaron aleatoriamente a dos grupos de diez ratas por grupo. Se administraron 10 mg/kg del grupo de tratamiento con paclitaxel a ratones por vía intraperitoneal (i.p.) 4, 9 y 14 días. El día 15 se sacrificaron los animales y se extrajeron los tejidos tumorales. Las secciones de tumor sólido incluidas en parafina se tiñeron con hematoxilina y eosina y tricrómico de Masson. También se tiñeron inmunohisto-químicamente secciones de tumor sólido con Netrin1 y Factor 8. Se aplicó el método Tunel para determinar la apoptosis. El paclitaxel aplicado como tumor sólido terapéutico de Ehrlich redujo el volumen de tumores en los grupos de tratamiento. Al final de los experimentos, en los grupos de tratamiento se redujo significativamente la expresión de Netrin 1 y la densidad de microvasos en comparación con el grupo control. Además, el paclitaxel en el grupo tratamiento aumentó el número de células apoptóticas. Sugerimos que la disminución de la expresión de Netrin 1 reduciría la densidad de los vasos y aumentaría la apoptosis.

Advances of research on CAR-T cell immunotherapy for solid tumors / 中国药科大学学报

@#Adoptive cellular immunotherapy has been widely recognized in recent years due to its remarkable results, especially the success of CD19-specific chimeric antigen receptor (CAR) autologous T cell therapy for malignant hematoma. Previous studies have found the existence of tumor immune microenvironment, heterogeneous targets, and immunosuppressive receptors in solid tumors, which has led to the shortcomings of CAR-T treatment of solid tumors. This article proposes the methods to improve CAR-T cells to increase T cell infiltration, co-expression of cytokines and enzymes and modification of related receptors in order to enhance the anti-solid tumor activity of CAR-T, laying a theoretical foundation for the follow-up CAR-T cell treatment of solid tumors.

T lymphocyte homing: a critical factor of adoptive cell therapy for solid tumors / 中国肿瘤生物治疗杂志

@#[Abstract] In recent years, tumor immunotherapy has developed rapidly, among which T-cell-based adoptive cell therapy has achieved certain clinical effect and become one of the most potential immunotherapeutics. T cell infiltration mainly includes rolling, adhesion, extravasation and chemotaxis etc. However, there are physical barriers, chemokine mismatch, vascular abnormalities, immunosuppressive microenvironment and other factors that limit the efficacy of adoptive cell therapy. The homing ability of T cells can be further improved by optimizing the chemokine receptor on the cell surface, inserting targeted peptide, improving the way of administration, and adopting combined treatment of radiotherapy, immune checkpoint blocker, tumor vaccine and bispecific antibody, etc. This review mainly summarizes the process of T cell infiltration, the influencing factors of T cell targeting tumor site and the relevant treatment strategies, as well as gives a prospection for future research.

Evaluation of spirometry as a parameter of response to chemotherapy in advanced lung cancer patients: A pilot study

Context: Spirometry is an important tool to monitor treatment response in diseases such as chronic obstructive pulmonary disease and asthma. However, there is lack of evidence to support its application to evaluate response to chemotherapy in advanced lung cancer. It might be a useful adjunct to the imaging-based response evaluation which lacks functional assessment of lungs. Aims: The study was conducted to evaluate the change in spirometry in lung cancer patients after chemotherapy and to find its correlation with change in physical tumor size. Subjects and Methods: Sixty-two advanced lung cancer patients who were eligible for palliative chemotherapy were enrolled. Baseline tumor size evaluation using Response Evaluation Criteria in Solid Tumor (RECIST)-based scoring system, and spirometry was done. Four cycles of double agent (platinum doublets) chemotherapy were administered, after which treatment response was evaluated. Repeat spirometry was analyzed and correlated with changes in physical tumor size. Results: Twenty-five patients showed a response (all partial response) to four cycles of chemotherapy. Small cell carcinoma showed a better response rate than non-small cell carcinoma (78% vs. 39%). There was statistically significant improvement in forced expiratory volume in 1 (FEV1) (P = 0.01) and forced vital capacity (P = 0.03) in responders as compared to nonresponders. Change in FEV1 showed a statistically significant correlation with the change in tumor size (RECIST score) (r = –0.34; P = 0.04). Conclusions: Improvement in spirometry correlates with the tumor response as judged using RECIST criteria after chemotherapy. Further studies with bigger sample size are required to consolidate the results

Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer

Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors. As downstream effectors of the mammalian Hippo pathway, YAP and/or TAZ (YAP/TAZ) are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2 (LATS1/2)-MOB kinase activator 1 (MOB1) complex, which restricts the transcriptional activity of YAP/TAZ. However, dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes, most of which are closely related to cancer. Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia, describe current agents and therapeutic strategies targeting the hypoxia-YAP/TAZ axis, and highlight questions that might have a potential impact in the future.

Current status and challenges of TCR-T therapy in solid tumor / 中国肿瘤生物治疗杂志

@#[Abstract] T cell receptors (TCR) are specifically expressed on T cell surface, which can recognize different tumor antigens to kill and scavenge cancerous cells. TCR-engineered T cells (TCR-T) therapy is to harbor TCR specific to tumor cells and modify the T cells with genetic engineering techniques to achieve the purpose of treating tumors after transfusion. Despite some achievements in TCR-T therapy, there are still some problems, such as treatment toxicity, limited T cell infiltration and antigen-specific deficiency and so on. So, the safety and effectiveness of TCR-T therapy need to be constantly optimized. Therefore，this paper summarizes the research status of TCR-T therapy for solid tumors in domestic and overseas, as well as the existing problems and countermeasures.

Evaluation of the antioxidant potential of Copaifera multijuga in Ehrlich tumor-bearing mice

Copaifera multijuga, commonly known as copaiba, is popularly used in the form of tea for various conditions due to the presence of antioxidant substances in its composition, which protect cells against damage caused by free radicals. Its oleoresin is also used as an anti-inflammatory and antitumoral agent. The present study investigated the antioxidant effect of the ethanolic extract of copaiba stem bark on Swiss mice inoculated with solid Ehrlich tumors. Mice were inoculated subcutaneously with 1x106 Ehrlich's tumor cells and treated via gavage with ethanolic extract of copaiba for thirty days, with doses varying between 100 and 200 mg kg-1. Biochemical analyses of enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)], non-enzymatic antioxidants [reduced glutathione (GSH) and ascorbic acid (ASA)], substances reactive to thiobarbituric acid (TBARS) and protein carbonylation (carbonyl) in different tissues were significantly affected. The extract administered at 200 mg kg-1 presented higher antioxidant capacity in the liver, increased CAT, GST, GSH and decreased TBARS, as well as increased CAT activity and protein carbonylation in brain tissue. The results showed that the copaiba extract was able to reverse the oxidative stress caused by solid Ehrlich tumor, probably due to the presence of antioxidant compounds, and had potential antineoplasic effect after a 30-day treatment. (AU)

Updated developments on molecular imaging and therapeutic strategies directed against necrosis

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.

Impact of solid tumor history on treatment response and survival of patients with diffuse large B-cell lymphoma / 中华血液学杂志

Objective@#To observe whether the history of solid tumors affects the treatment response and survival situation of patients with diffuse large B-cell lymphoma (DLBCL) .@*Methods@#A retrospective study was conducted in 836 patients with DLBCL who were treated in the Department of Hematology at Ruijin Hospital from 2013 to 2018. Among them, 34 DLBCL patients who had the history of solid tumors were classified into double cancer group. From 802 patients without history of solid tumors, 68 DLBCL patients were selected as control group, using 1∶2 matching on propensity scores for age, gender, IPI score and etc. All patients included in the study had follow-up interviews through medical record and telephone for mortality from any cause. Treatment response and 3-year overall survival (OS) and progression-free survival (PFS) of two groups were analyzed.@*Results@#The complete remission rates after RCHOP (Rituximab+Cyclophosphamide+Vincristine+Adriamycin 50 mg/m2 or Epirubicin or Liposome Adriamycin+Prednisone) regimen were 79.4% and 67.6% in the double cancer group and the control group, respectively (P=0.210) . Among the 102 patients, 6 patients died in the double cancer group while 24 patients died in the control group and the median survival time of both two groups were not reached. The 3-year OS were (74.7±9.5) % and (63.5±6.1) % (χ2=2.791, P=0.095) , while 3-year PFS were (72.1±8.8) % and (54.3±6.4) % (χ2=1.400, P=0.237) in the double cancer group and the control group, respectively.@*Conclusion@#The history of solid tumors didn’t affect DLBCL patients’ treatment response and short-term survival.

The influence of self-efficacy on parenting stress among parents of children with malignant solid tumors / 中国实用护理杂志

Objective@#To explore the effect of self-efficacy on parenting stress among parents of children with malignant solid tumors.@*Methods@#Totally 100 parents of children with malignant solid tumors were investigated and analyzed by using the general questionnaire, parenting stress Index-Short Form(PSI-SF) and General Self-Efficacy Scale (GSES).@*Results@#The score of general self-efficacy for parents was 1.93±0.54, and the total score of parenting stress was 111.84±13.36. The general self-efficacy and parenting stress scores of parents with malignant solid tumors were significantly negatively correlated with the scores of parental misery, parent-child relationship and difficult children (r=-0.72, -0.65, -0.62 -0.55, all P<0.01). Hierarchical logistic regression analysis indicates that the parenting stress was influenced by self-efficacy, the gender of parents, education level and whether or not on position.@*Conclusions@#Self-efficacy is one of the most critical influencing factors on parenting stress of parents.A new approach to improve the self-efficacy is to be achieved to reduce the parenting stress level among parents of children with solid tumors.

BiTE-T：Anovel gene-editing T cell for solid tumor therapy / 中国肿瘤生物治疗杂志

@#Gene-engineered T cells, represented by chimeric antigen receptor T cells (CAR-T cells), have achieved great success in hematological tumors, and gradually been applied in the clinical treatment of tumors. In 2017, two CD19-CAR products for hematological tumors were consecutively approved for marketing in America, and have shown powerful anti-tumor efficacy in non-solid tumor treatment. However, CAR-T cell therapy didn’t achieve expectant therapeutic efficacy in solid tumors due to complicated tumor microenvironment and restriction of surface tumor antigen. In addition, the cytotoxicity caused by off-target effects is more troublesome. To address these hurdles, more and more researchers have begun to explore new gene-edited T cells for solid tumor treatment, among which bispecific T cell engager T cell (BiTE T) has shown high anti-tumor efficacy in vitro evaluation and in vivo animal models and thus has attracted great attention. This review mainly discusses the current difficulties confronted by solid tumor treatment and the principles, characteristics and advantages of BiTE-T cell preparation.

Homing barriers and solutions for CAR-T cells in the treatment of solid tumors / 中国肿瘤临床

Chimeric antigen receptor T (CAR-T) cell therapy is an emerging immunotherapy that has allowed for major breakthroughs in the treatment of hematological neoplasms. However, little progress has been made in the treatment of solid tumors, primarily due to the difficulty in homing to tumor tissues by CAR-T cells during treatment. The complex tumor microenvironment and the barrier function of tumor tissues prevent CAR-T cells from contacting tumor cells, thereby preventing them from exerting their antitumor ac-tivity. This review article summarizes not only the progress made in the study of homing disorders of CAR-T cells in the treatment of solid tumors but also the current methods to overcome these disorders.