Head and neck squamous cell carcinoma(HNSCC) associated with a poor prognosis and diminished quality of life for patients is the most prevalent pathological type among head and neck tumors. Currently,the standard treatment modalities comprise systemic therapies(including chemotherapy,targeted therapy,and immunotherapy) and local therapies(surgery and radiotherapy).Immunotherapy,characterized by high specificity and low toxicity,is progressively expanding from advanced palliative care to the stage of locally advanced curative treatment and has demonstrated promising efficacy.This review summarizes the latest advances in immunotherapy for HNSCC,aiming to provide reference for optimizing clinical management strategies and facilitating the clinical research.
Humans ; Immunotherapy/methods* ; Head and Neck Neoplasms/immunology* ; Squamous Cell Carcinoma of Head and Neck/therapy*

OBJECTIVE: To investigate the predictive role of the modified Endothelial Activation and Stress Index (mEASIX) in the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy and cytokine release syndrome (CRS). METHODS: The clinical data of 70 relapsed and refractory (R/R) B-cell tumor patients who were treated with CAR-T therapy from September 1, 2018 to February 28, 2023 in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, were retrospectively analyzed. The value of log-2 mEASIX before conditioning (-7 d) was calculated, and the patients were divided into a low-mEASIX group (42 patients) and a high-mEASIX group (28 patients) based on the cut-off value of 5.443 determined by the receiver operating characteristic (ROC) curve. Eventually, the predictive role of mEASIX before conditioning on the efficacy of CAR-T cell therapy and CRS was analyzed. RESULTS: The high-mEASIX group exhibited significantly worse median overall survival (OS) and median progression-free survival (PFS) in comparison to the low mEASIX group (OS: 3.2 months vs not reached, P < 0.01; PFS: 1.3 months vs 6.0 months, P =0.009). The incidence of grade ≥2 CRS in the high-mEASIX group was substantially higher than that in the low-mEASIX group (57.1% vs 19.0%, P =0.007). The degree of remission after CAR-T therapy (P =0.001), whether CRS occurs or not (P =0.041), the lactate dehydrogenase (LDH) level before conditioning (P =0.046), and the mEASIX score before conditioning (P =0.047) were independent influencing factors for the OS of patients receiving CAR-T cell therapy. CONCLUSION The mEASIX score before conditioning can predict OS and the incidence of grade ≥2 CRS in patients with relapsed and refractory B-cell tumors who receive CAR-T cell therapy.
Cytokine Release Syndrome/therapy* ; Immunotherapy, Adoptive/methods* ; Humans ; Lymphoma, B-Cell/therapy* ; Retrospective Studies ; Hematology ; China ; Receptors, Chimeric Antigen/blood* ; Predictive Value of Tests

Despite the groundbreaking advances in cancer immunotherapy achieved by immune checkpoint inhibitors (ICIs), their efficacy remains limited by the immunosuppressive tumor microenvironment (TME). Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key effectors of the Hippo signaling pathway, play pivotal roles in tumor immune evasion. They directly regulate the expression of immune checkpoints, mediate the formation of an immunosuppressive microenvironment, inhibit T cell function, and interact with other signaling pathways to promote immune escape. Diverse strategies targeting YAP/TAZ have been developed, including direct inhibition, modulation of upstream regulators, and suppression of downstream target genes. Preclinical studies have demonstrated that combining YAP/TAZ inhibition with ICIs significantly enhances therapeutic efficacy across various tumor models. This review summarizes recent advances in understanding the role of YAP/TAZ in immune evasion within the TME and explores the potential of targeting this pathway to improve immunotherapy outcomes. Furthermore, it discusses the translational value of combination therapies based on YAP/TAZ inhibition, providing a theoretical framework and practical guidance for the development of innovative immunotherapeutic strategies and precision medicine approaches.
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Humans ; Immunotherapy/methods* ; Neoplasms/metabolism* ; Signal Transduction/drug effects* ; Adaptor Proteins, Signal Transducing/immunology* ; Animals ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; Transcription Factors/immunology* ; YAP-Signaling Proteins ; Tumor Microenvironment

In epidemiological statistics, the incidence rate and mortality rate of malignant lung tumors rank among the top. Non-small cell lung cancer (NSCLC) constitutes an important part of lung cancer and has become a key focus of clinical research and treatment. Among the genomic characteristics of NSCLC, the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is one of the main tumor drivers, accounting for approximately 25% of all NSCLC cases. The existence of this mutation is closely related to the treatment response and prognosis of patients. Therefore, the treatment strategy for KRAS-mutated NSCLC is an important topic in the field of tumor research. In the current era, immunomodulatory therapy has rapidly gained popularity and developed rapidly in oncology due to its unique mechanism of action and remarkable clinical efficacy. The treatment strategies targeting the KRAS-mutated of NSCLC have gradually become a research hotspot. The advent of immune checkpoint inhibitors (ICIs) has opened up a new therapeutic avenue for patients with such cancers, and clinical studies have shown significant effects in improving survival rates. Nevertheless, there are still many challenges in the application of immunotherapy, such as the complexity of the tumor microenvironment, individual differences among patients, and drug resistance mechanisms. This article reviews the progress of immunotherapy for KRAS-mutated NSCLC, focusing on the specific application of immunotherapy, the exploration of combination therapies, and the results of related clinical trials. At the same time, it discusses the possible future development directions of KRAS-mutated NSCLC treatment, providing a reference for clinical treatment practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Lung Neoplasms/immunology* ; Proto-Oncogene Proteins p21(ras)/immunology* ; Immunotherapy/methods* ; Mutation ; Animals

Small cell lung cancer (SCLC) is the thoracic malignant tumor and accounts for about 15% of lung malignancies and transfer often occurs by the time of diagnosis. Extensive stage-small cell lung cancer (ES-SCLC) accounts for about 2/3 of all SCLC. For many years, radiotherapy has occupied an important position in the treatment of SCLC, especially in the treatment of ES-SCLC, because SCLC is more sensitive to radiotherapy. However, in recent years, immune checkpoint inhibitor has shown more excellent antitumor activity in the treatment of ES-SCLC and become the mainstream argument for the treatment of ES-SCLC. However, will radiotherapy be buried by the times among the therapeutic approaches for ES-SCLC? In this article, we will review the clinical progress of radiotherapy, immunotherapy and combination therapy for ES-SCLC.
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Humans ; Small Cell Lung Carcinoma/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy ; Neoplasm Staging ; Radiotherapy/methods* ; Combined Modality Therapy

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
Stomach Neoplasms/genetics* ; Humans ; Precision Medicine/methods* ; China ; Immunotherapy/methods*

Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade (ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified; some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration (FDA) for clinical treatment. However, limited responses and immune-related adverse events (irAEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoplasms/drug therapy* ; Immunotherapy/methods* ; Animals

Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in treating hematological malignancies and is expanding into other indications such as autoimmune diseases, fibrosis, aging and viral infection. However, clinical challenges persist in treating solid tumors, including physical barriers, tumor heterogeneity, poor in vivo persistence, and T-cell exhaustion, all of which hinder therapeutic efficacy. This review focuses on the critical role of tonic signaling in CAR-T therapy. Tonic signaling is a low-level constitutive signaling occurring in both natural and engineered antigen receptors without antigen stimulation. It plays a pivotal role in regulating immune cell homeostasis, exhaustion, persistence, and effector functions. The "Peak Theory" suggests an optimal level of tonic signaling for CAR-T function: while weak tonic signaling may result in poor proliferation and persistence, excessively strong signaling can cause T cell exhaustion. This review also summarizes the recent progress in mechanisms underlying the tonic signaling and strategies to fine-tune the CAR tonic signaling. By understanding and precisely modulating tonic signaling, the efficacy of CAR-T therapies can be further optimized, offering new avenues for treatment across a broader spectrum of diseases. These findings have implications beyond CAR-T cells, potentially impacting other engineered immune cell therapies such as CAR-NK and CAR-M.
Humans ; Immunotherapy, Adoptive/methods* ; Receptors, Chimeric Antigen/immunology* ; Signal Transduction/immunology* ; T-Lymphocytes/immunology* ; Neoplasms/immunology* ; Animals

B lymphocytes (B cells) play a complex and paradoxical role in tumorigenesis. They can recognize tumor-associated antigens, present these antigens to T cells, and produce antibodies that directly target and eliminate tumor cells. This makes B cells a potentially powerful ally in combating cancer. However, B cells also exhibit immunosuppressive functions, secreting cytokines like IL-10 or generating tumor-promoting antibodies that dampen the anti-tumor immune response, and some tumor cells have even been shown to exploit B cells to promote their growth and metastasis. This dual nature of B cells presents both opportunities and challenges for tumor immunotherapy. In this review, we summarize the mechanisms underlying the multifaceted functions of B cells and their current applications in cancer immunotherapy. Furthermore, we also explore the key issues and future directions in this field, emphasizing the need for further research to fully harness the anti-tumor potential of B cells in the fight against cancer.
Humans ; B-Lymphocytes/immunology* ; Neoplasms/therapy* ; Carcinogenesis/immunology* ; Immunotherapy/methods* ; Animals

Therapeutic cancer vaccines have experienced a resurgence over the past ten years. Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle, primarily by activating the immune system to promote tumor regression and overcome immune resistance. In this review, we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle, including the effector cell function, infiltration, initiation, and exhaustion. We summarize the identification of tumor antigens and their delivery through cancer vaccines. We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy. Additionally, the impact of aging and myelosuppression, two prevalent forms of immunological stress, on the effectiveness of therapeutic cancer vaccines is deliberated. Finally, we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
Humans ; Cancer Vaccines/therapeutic use* ; Neoplasms/therapy* ; Immunotherapy/methods* ; Antigens, Neoplasm/immunology* ; Animals