Multidimensionally Decoding the Impact of Tumor Heterogeneity on Immunotherapy Responsiveness in Gastrointestinal Tumors

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About this Research Topic

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Background

In recent years, the incidence of gastrointestinal tumors has been increasing, but their outcomes have not been significantly improved. The mortality rates of colorectal cancer, stomach cancer, and esophageal cancer rank second, fourth, and sixth among tumor-related deaths, respectively. The advent of immunotherapy has shed light on solid tumors, yet only about 20% of patients experience sustained responses. In addition, the expensive price and high incidence of immune-related adverse events (irAEs) urgently require our ability to identify immunotherapy-responsive patients early.

With the popularization of immunotherapy, it is generally recognized that the strong inter-tumor heterogeneity leads to divergent responsiveness to immunotherapy in patients with the same histological type. For multifocal tumors, the presence of intra-tumor heterogeneity even leads to the response of some lesions to immunotherapy, and some are ineffective. In view of this, existing biomarkers including PD-L1, TMB, dMMR, and MSI, are far from meeting the needs of clinicians for precision medicine.

Recent advances in comprehensive analysis techniques of single-cell multi-omics, spatial transcriptomics, and bulk multi-omics sequencing have shown the potential to guide precision immunotherapy. It is urgent to integrate high-resolution single-cell sequencing, bulk multi-omics sequencing with larger sample size, and transferable proteogenomic technologies to investigate the impact of tumor heterogeneity on immunotherapy responsiveness, so as to develop novel biomarkers and individualized immunotherapy strategies.

The Research Topic aims to introduce recent advances in the field of immunotherapy for gastrointestinal tumors and explore the impact of tumor heterogeneity on differentiated immunotherapy responses from multiple dimensions using increasingly mature single-cell multi-omics and spatial transcriptomics technologies, combined with bulk multi-omics sequencing technology with rich sample sizes and clinical information. Meanwhile, we look forward to these studies providing new insights into identifying immunotherapy-sensitive patients, reducing irAEs, and improving the efficacy of immunotherapy. Submissions may focus on, but are not limited to, the following:
1. Combined with single-cell, spatial transcriptomics, and bulk sequencing data to investigate the heterogeneous microenvironment landscape behind differentiated immunotherapy.
2. Integrate multi-dimensional, multi-technology platforms to decode influencing factors, potential mechanisms, and interventions for immunotherapy non-responsive patients.
3. Multidimensional development and validation of biomarkers to identify immunotherapy-sensitive populations early, predict survival, and serve for individualized immunotherapy.
4. Developing novel combination therapy strategies to improve efficacy and reduce irAEs.
5. Multi-center Clinical Trials or Meta-Analysis to explore the heterogeneous immunotherapy response and its influencing factors in gastrointestinal tumors.
6. Case report, Comments, or Reviews on novel strategies for immune combination therapy in gastrointestinal tumors.

Please NOTE: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope for this section and will not be accepted as part of this Research Topic.

Keywords: Tumor Heterogeneity, Immunotherapy Responsiveness, Gastrointestinal Tumor

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