About this Research Topic

Background

Gastrointestinal tumors are a heterogeneous disease setting, covering colorectal, gastric, esophageal, pancreatic and liver cancers, and are still the most common causes of cancer-related death worldwide. Despite the improvement in chemoradiotherapy, surgery and targeted therapies alike, the overall 5-years survival rate of gastrointestinal cancer patients remains less than 15%. The difficulties in early diagnosis, the rapid progression of the disease and the resistance to therapies render the necessity to develop new personalized therapies a high priority. In recent years, immunotherapy-based agents undoubtedly opened new therapeutic opportunities in fighting these cancers. Nevertheless, the assessment of microsatellite instability status and expression of immune checkpoint molecules have not been established as sole biomarkers for the clinical practice of immunotherapy.

The goal of this Research Topic is to describe new potential immunological parameters which are mandatory for the development of a new age of precision oncology to treat gastrointestinal cancer patients with immunotherapies. These new biomarkers arise from two critical aspects of gastrointestinal cancers:
i) The heterogeneity of gastrointestinal tumors, if they affect either different tissues, or the same tissues.
ii) The complexity of the immune landscape of the tumor microenvironment. For example, some subclasses of colorectal cancers represent the so-called "hot tumors", while other cancers such as pancreatic ductal adenocarcinoma represent the "cold tumors". Overall, cold tumors show a low activation of the immune system and tend to not respond to immunotherapy. For this class of tumors, which represent up to 80% of all cancers, it is necessary to identify predictive biomarkers and/or new targets of non-canonical immunotherapy.
iii) The clinical use of conventional immunotherapeutic agents (i.e. immune checkpoint, such as PD-1/PD-L1 and CTLA-4, inhibitors) has paved the way for a new era of anti-cancer strategies being developed. Indeed, many other soluble checkpoints, such as soluble B7-H3 and CD80, are currently under investigation. Of the wide range of receptors expressed by immune cells, many other molecules profoundly influence the activation status of the immune system: for instance, cytokines, vesicles and tumor-derived soluble factors, which are promising candidates as potential biomarkers or new targets for more effective immunotherapies.

Even if immunotherapy has significantly improved the quality of life of patients with malignancies in the last decade, many mechanisms of primary and acquired resistance are still unknown and urgently need to be identified. This Research Topic aims to uncover new insights in immunotherapy strategies in the clinic management of gastrointestinal cancer patients. We encourage authors to submit manuscripts focused on by not limited to:
- Soluble cytokines and chemokines with potential beneficial outcomes in GI cancers
- Soluble immune checkpoints as clinical biomarkers and therapeutic targets
- Circulating cells of relevance in GI cancers
- Circulating DNA and its role as a therapeutic target or biomarker

Studies including basic research, translational research, and clinical research are welcomed. We accept “original research”, “systematic reviews”, “meta-analysis”, “reviews”, “clinical trial”, and “brief research report”. Other types of manuscript will be evaluated by the editors before further consideration.

Important Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.

Keywords: Circulating biomarkers, Soluble factors, cytokines, chemokines, immune checkpoints, Circulating cells, Circulating DNA, Immunotherapy, Gastrointestinal cancer

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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