Jia Yi , Sangmu Quji , Luxuan Guo , Zhongqiu Chai , Xianbin Kong , Jingyan Meng
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引用次数: 0
Abstract
Colorectal cancer (CRC), ranking as the third most prevalent malignant tumor globally (accounting for 10.0 % of new cancer cases) and the second leading cause of cancer-related deaths (9.4 % of cancer mortality), continues to escalate in incidence, posing a significant threat to human health. Although conventional therapies such as surgery, radiotherapy, and chemotherapy remain the clinical mainstay, their efficacy in improving patient survival and quality of life has reached a plateau, necessitating the exploration of novel therapeutic approaches. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a highly promising approach for cancer treatment. Notably, the complexity of the solid tumor microenvironment (TME) presents challenges for the application of CAR-T therapy in CRC, including antigen heterogeneity, immune suppression, and off-target toxicity. However, the development of multi-target CAR-T cells and their combination with immunomodulatory drugs holds significant clinical potential. Furthermore, in recent years, oncolytic virus (OV) therapy has garnered substantial attention due to its unique antitumor mechanisms. Our study demonstrates that OVs can precisely target CRC tissues, inducing tumor cell apoptosis through selective infection and intracellular replication while concurrently activating systemic antitumor immune responses and inhibiting angiogenesis, thereby achieving multidimensional therapeutic effects. Further investigations reveal that OVs can serve as gene delivery vectors for therapeutic molecules or synergize with chimeric antigen receptor T-cell (CAR-T) therapy and immune checkpoint inhibitors to significantly enhance treatment efficacy. Simultaneously, gut microbiota, a critical regulator of CRC progression, can influence both CAR-T and OVs therapies through metabolic modulation and immune remodeling. Building upon these mechanisms, this review innovatively proposes a tripartite “OVs-gut microbiota-CAR-T" strategy: OVs may reprogram the immunosuppressive TME and release tumor antigens to enhance CAR-T infiltration and activity, while concurrent modulation of gut microbiota could further alleviate immunosuppression and reduce treatment toxicity, establishing a bidirectional synergistic loop. This interdisciplinary integration strategy may provide a groundbreaking approach to overcome current therapeutic limitations in CRC and advance precision tumor immunotherapy to new frontiers.
期刊介绍:
Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered.
Research Areas include:
• Antigen receptor sites
• Autoimmunity
• Delayed-type hypersensitivity or cellular immunity
• Immunologic deficiency states and their reconstitution
• Immunologic surveillance and tumor immunity
• Immunomodulation
• Immunotherapy
• Lymphokines and cytokines
• Nonantibody immunity
• Parasite immunology
• Resistance to intracellular microbial and viral infection
• Thymus and lymphocyte immunobiology
• Transplantation immunology
• Tumor immunity.