This Research Topic is part of the “Methods in Immunology” series. Please submit your article to the Research Topic that best suits the focus of your research. Introduction and general guidelines: This series aims to highlight the latest experimental techniques and methods used to investigate fundamental questions in Immunology research, with a focus on Cancer Immunity and Immunotherapy.

At present, less than 30% of researchers worldwide are women. Long-standing biases and gender stereotypes are discouraging girls and women away from science-related fields, and STEM research in particular. Science and gender equality are, however, essential to ensure sustainable development as highlighted by UNESCO. In order to change traditional mindsets, gender equality must be promoted, stereotypes defeated, and girls and women should be encouraged to pursue STEM careers. Therefore, Frontiers in Immunology is proud to offer this platform to promote the work of women scientists, across all fields of Cancer Immunity and Immunotherapy.

Gastrointestinal cancers are among the most prevalent malignancies worldwide, with high rate of global cancer incidence and cancer-related death. Gastrointestinal cancers include esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, and liver cancer, which all, except the last one, are covered in this volume. The fourth volume of the “Interdisciplinary Cancer Research” series, entitled “Gastrointestinal Cancers: An Interdisciplinary Approach” publishes comprehensive volumes on mechanisms of gastrointestinal cancers and novel immunotherapy opportunities and presents the most updated and peer-reviewed chapters on gastrointestinal cancers therapy. This interdisciplinary series is of special value to researchers working on cell biology, immunology, biochemistry, genetics, and practitioners working on oncology and gastroenterology. This is the main concept of Cancer Immunology Project (CIP), which is a part of Universal Scientific Education and Research Network (USERN). This interdisciplinary book will be of special value for researchers, oncologists, and gastroenterologists who wish to extend their knowledge on gastrointestinal cancers.

Immune checkpoint inhibitors (ICIs) such as anti-PD-1 and anti-PD-L1 antibodies are highly effective against many types of cancer, yet durable responses are limited to a subset of patients highlighting the need for the development of effective biomarkers to predict prognosis and efficacy. Currently, PD-L1 expression in tumors, microsatellite instability (MSI) or mismatch repair deficiency (dMMR), and tumor mutation burden (TMB) are known as biomarkers for cancer immunotherapy but are not sufficient. Combination therapy with immune checkpoint inhibitors and chemotherapy or radiation therapy, as well as diverse therapies targeting intra-tumoral regulatory T cells have been described, but there are currently no unifying biomarkers that are applicable to clinically, a simple, fast, non-invasive method that can yield biomarkers of disease with a minimal adverse effect on patients is desirable. Recent findings suggest that the balancing of effector T cells and regulatory cells in the tumor microenvironment is associated with cancer progression and prognosis. Cells and molecules involved in the control of cancer are complex, and a better understanding of the tumor immune environment will lead to the development of truly effective biomarkers. This topic will focus on novel biomarkers that predict efficacy, prognosis, or the development of adverse events in various cancer immunotherapies, and extensive basic research leading to the development of biomarkers. 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 topic. We expect a wide range of research, not only in serology, genetics, and immunocytochemistry but also in bacterial flora. Research on the development of novel assays and bioinformatics methods is also welcome: • Non-invasive biomarkers for cancer immunotherapy. • Bulk RNA-seq, scRNA-seq, or Rep-seq methods. • Correlation of tumor immune cells with gut microbiota in tumor immunotherapy. • Impact of Teff and Treg balance in the tumor microenvironment on tumor prognosis. • Inflammatory and immune signatures associated with drug response versus resistance in cancer.

Immunotherapy has revolutionized the treatment of malignancies. Targeting of immune checkpoints cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 (PD-1) and its ligand (PD-L1) has led to improving survival in a subset of patients. Despite their remarkable success, clinical benefit remains limited to only a subset of patients. A significant limitation behind these current treatment modalities is an irregularity in clinical response, which is especially pronounced among checkpoint inhibition. Currently, relevant predictors of cancer immunotherapy response include microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR), expression of PD-L1, tumor mutation burden (TMB), immune genomic characteristics, and tumor infiltrating lymphocytes (TILs). However, none of them have sufficient evidence to be a stratification factor. Moreover, as the combined strategies for effective cancer immunotherapy had been developed in multiple tumors, such as Immunotherapy combined with chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. Therefore, the development of novel biomarkers endowed with high sensitivity, specificity and accuracy able to identify which patients may truly benefit from the treatment with cancer immunotherapy would allow to refine the therapeutic selection and to better tailor the treatment strategy.