Abstract
Gastrointestinal cancer is a leading cause of cancer-related mortality and remains a major challenge for cancer treatment. Despite the combined administration of modern surgical techniques and chemoradiotherapy (CRT), the overall 5-year survival rate of gastrointestinal cancer patients in advanced stage disease is less than 15%, due to rapid disease progression, metastasis, and CRT resistance. A better understanding of the mechanisms underlying cancer progression and optimized treatment strategies for gastrointestinal cancer are urgently needed. With increasing evidence highlighting the protective role of immune responses in cancer initiation and progression, immunotherapy has become a hot research topic in the integrative management of gastrointestinal cancer. Here, an overview of the molecular understanding of colorectal cancer, esophageal cancer and gastric cancer is provided. Subsequently, recently developed immunotherapy strategies, including immune checkpoint inhibitors, chimeric antigen receptor T cell therapies, tumor vaccines and therapies targeting other immune cells, have been described. Finally, the underlying mechanisms, fundamental research and clinical trials of each agent are discussed. Overall, this review summarizes recent advances and future directions for immunotherapy for patients with gastrointestinal malignancies.
Highlights
Gastrointestinal (GI) cancers are among the top 10 most prevalent and deadliest tumors worldwide, accounting for 26% of global cancer incidence and 35% of all cancer-related deaths [1]
Advances in Gastrointestinal Cancer Immunotherapy immunotherapy mainly based on checkpoint inhibitors has shown great prospects in clinical research, which shows the importance of immunotherapy in cancer treatment
In accordance with some studies, transforming growth factor beta (TGF-b) and other growth factors secreted by cancer-associated fibroblasts (CAFs) promoted the proliferation of colorectal cancer (CRC) cells through the Smad2/Smad4 pathway [38] and MAPK/PI3K/AKT pathway [39]
Summary
Gastrointestinal (GI) cancers are among the top 10 most prevalent and deadliest tumors worldwide, accounting for 26% of global cancer incidence and 35% of all cancer-related deaths [1]. Surgical resection remains the primary treatment option for patients with colorectal cancer (CRC), gastric cancer (GC) and esophageal cancer (EC). Over the last few decades, immune-targeted therapy has emerged as a revolutionary option for cancer treatment [3]; the regulatory role of the immune system underlying GI cancers remains to be clarified. Advances in Gastrointestinal Cancer Immunotherapy immunotherapy mainly based on checkpoint inhibitors has shown great prospects in clinical research, which shows the importance of immunotherapy in cancer treatment. We outline the functional and molecular basis of oncoimmunology, with an emphasis on novel immune checkpoint targets and examples of applications in both laboratory research and clinical trials. We hope that this review will bring new insight into cancer immunotherapy for oncologists and immunologists
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