Gastrointestinal (GI) cancers, including gastric cancer, colon cancer, liver cancer, esophageal cancer, and pancreatic cancer, seriously threaten the health of human beings worldwide with a high rate of morbidity and mortality. The clinical successes achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 have opened a new cancer therapy era and brought new hope to cancer patients. However, the overall response rate (ORR) of ICI monotherapy in the non-selective population is only about 20%, in which some patients subsequently develop immunotherapy resistance. Moreover, the remaining 70-80% of patients displayed primary resistance to ICIs, and a few patients even experienced hyper progression disease (HPD). Although PD-L1 expression, mismatch repair deficient (MMRd), high tumor mutational burden (TMB-H) , high homologous recombination deficiency (HRD), and tumor infiltrated immune cells (TILs) are known as effective biomarkers for immunotherapy, growing studies have reported that ICIs could not improve the OS of all patients with PD-L1 expression higher than 50%, and the ORR of MSI-H patients was only about 60%, whereas some patients with low PD-L1 expression or MSS could still benefit from immunotherapy, indicating the complexity of ICI resistance. Therefore, it is of great importance and significance to explore the prediction biomarkers for primary or acquired immunotherapy resistance and elucidate their underlying molecular mechanisms and develop reversal strategies. Due to the multiple steps of the cancer immune cycle and complex immune microenvironment, any disorders of immune cell infiltration or T cell activation, such as lack of antigens and/or their presentation, lack of response to antigen presentation, and T cell priming, could contribute to ICI resistance. The combination with anti-angiogenesis therapy, radiotherapy, chemotherapy, and other ICIs has improved the efficacy of ICI therapy to some extent in the clinic. Although numerous studies related to ICI resistance were reported in GI cancers, due to the strong spatial/temporal heterogeneity and the complex immune microenvironment in different kinds of GI cancers and different individuals, many questions about ICI resistance and reversal strategies remain unsolved. The aim of this Research Topic is to provide a forum to exhibit the latest research achievement related to the exploration of biomarkers for immunotherapy resistance including HPD and the underlying molecular mechanisms, as well as the development of reversal strategies in GI cancers. We hope this Research Topic will lead to a better understanding of precision cancer immunotherapy and provide useful clues for clinical application to benefit more GI cancer patients with immunotherapy.

This book explores the relationship between the gut microbiome and cancer, illuminating various facets from fundamental roles to personalized therapies. It provides a comprehensive overview of the impact of the gut microbiome on cancer development, offering potential for innovative diagnostic and treatment approaches. The book discusses the role of dysbiosis in cancer development, the influence of the microbiome on treatment responses, and strategies to modulate the microbiome for enhanced therapies. It reviews the influence of the gut microbiome on immunotherapy resistance and chemoresistance in cancer patients. Additionally, the book presents gut microbiome biomarkers for cancer diagnosis and prognosis, the implication of the gut-brain axis on cancer development and progression, and the impact of diet and lifestyle on the microbiome. Towards the end, the book investigates the role of the gut microbiome in pediatric cancer and provides an outlook on the future challenges, technological advancements, and ethical considerations of gut microbiome research in the context of personalized cancer therapies. This book is intended for cancer researchers, medical oncologists, clinicians, pharmacologists, translational investigators, and medical students.

This volume discusses novel concepts in cancer biology, focusing on different factors that affect the tumor microenvironment. Topics covered include sex-based differences in the tumor microenironment, dormancy in the tumor microenvironment, the influence of obesity on the tumor microenvironment, and much more. Taken alongside its companion volumes, Tumor Microenvironment: Novel Concepts covers the latest research on various aspects of the tumor microenvironment, as well as future directions. Useful for introducing the newer generation of researchers to the history of how scientists studied the tumor microenvironment as well as how this knowledge is currently applied for cancer treatments, it will be essential reading for advanced cell biology and cancer biology students, as well as researchers seeking an update on research on the tumor microenvironment.

Traditionally, surgery, radiotherapy, chemotherapy and hormonal therapy have been used in clinical practice to treat cancer patients. However, these methods are either not completely tumor free or without collateral damage to health tissues. Therefore, tumor recurrence, partial remission, treatment side effect and poor tolerance in elderly patients, and lack of effective strategy to treat late-stage cancers have been the major hurdles faced by clinicians in health care. Although cancer immunotherapy including checkpoint blockade, CAR-T, oncolytic viruses, and recombinant cytokines has taken center stage in mainstream oncology because of its specifically targeting tumor cells without affecting surrounding normal cells, only a proportion of patients receiving treatment respond and others relapse after an initial response. Different tumor indications respond differently, and even in cancer types that respond, unresponsiveness are still observed. This resistance suggests that either lack of sufficient host recognition and immunity (intrinsic) or active immune suppression by tumor complex (acquired).