Reprogramming tumor immunity: microenvironment, immune escape, and innovative immunotherapeutic strategies

Cancer immunotherapy has transformed the treatment landscape for multiple malignancies; however, its clinical efficacy remains limited in many tumors due to complex mechanisms of immune resistance. Increasing evidence highlights the critical role of the tumor microenvironment in shaping antitumor immunity, with cancer-associated fibroblasts, hypoxia, metabolic reprogramming, and epigenetic regulation contributing to immune suppression and tumor immune escape. In addition, the microbiome has emerged as an important modulator of immunotherapy response, further emphasizing the systemic nature of immune regulation in cancer. Despite significant progress, major challenges persist, particularly in rare cancers and in tumors with intrinsic or acquired resistance to current treatments. The development of novel immunotherapeutic strategies, including cancer vaccines, adoptive cell therapies, bispecific antibodies, and oncolytic viruses, together with combination approaches involving chemotherapy, radiotherapy, or photodynamic therapy, offers new opportunities to improve therapeutic outcomes.Despite the remarkable progress achieved in cancer immunotherapy, many patients still fail to respond or eventually develop resistance, highlighting the need for a deeper understanding of the mechanisms that regulate antitumor immunity. Increasing evidence indicates that the tumor microenvironment plays a central role in determining therapeutic outcomes, as factors such as cancer-associated fibroblasts, hypoxia, metabolic reprogramming, and epigenetic modifications can promote immune evasion and limit the efficacy of current treatments. In addition, host-related factors, including the microbiome, have emerged as key modulators of immunotherapy response.This Research Topic aims to address these challenges by gathering contributions that explore the molecular and cellular mechanisms underlying immune regulation in cancer and that propose innovative therapeutic strategies to overcome resistance. Particular interest will be given to studies on novel immunotherapeutic approaches, such as cancer vaccines, adoptive cell therapies, bispecific antibodies, and oncolytic viruses, as well as combination therapies integrating immunotherapy with chemotherapy, radiotherapy, or photodynamic therapy. Through basic, translational, and preclinical research, this Topic seeks to identify new targets and therapeutic strategies to improve clinical outcomes, including in rare and therapy-resistant cancers.Reviews and original articles. • Cancer-associated fibroblasts (CAFs) and stromal regulation of antitumor immunity• Hypoxia, metabolic reprogramming, and immune suppression in the tumor microenvironment• Epigenetic mechanisms involved in tumor immune escape• Microbiome and host-related factors influencing immunotherapy response• Immunotherapy in rare, aggressive, or therapy-resistant cancers• Novel immunotherapeutic strategies, including cancer vaccines, adoptive cell therapies (CAR-T, TCR-T, TILs), bispecific antibodies, immune engagers, and oncolytic viruses• Combination therapies integrating immunotherapy with chemotherapy, radiotherapy, photodynamic therapy, or targeted therapies• Experimental models for immunotherapy research, including 3D cultures, organoids, and in vivo tumor models• Identification of new molecular targets to enhance antitumor immune responses• Translational and preclinical studies aimed at improving clinical outcomesPlease note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Topic editors: Natalia Belen Rumie Vittar, Paul J. Higgins Source: https://www.frontiersin.org/research-topics/79467/reprogramming-tumor-immunity-microenvironment-immune-escape-and-innovative-immunotherapeutic-strategies