Mechanism Explorations of Enhancing Immunotherapeutic Sensitivity via Mediating Immune Infiltration and Programmed Cell Death in Solid Tumor Microenvironment

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Background

Anti-tumor immunotherapy has ushered in a promising era for cancer treatments, solidifying its place as the primary therapeutic strategy for microsatellite unstable tumors, as recommended by the National Comprehensive Cancer Network's clinical guidelines. Yet, anti-tumor immunotherapy remains restricted to a specific group of patients, largely due to its strict indications and considerable side effects. Hence, it's imperative to devise appropriate strategies that broaden the scope of immunotherapy adaptation.

In the translational medicine approach, non-apoptotic programmed cell death (PCD) has been identified as being considerably linked with escalating tumor mutational burden (TMB) and immunotherapy response. Such as ferroptosis, pyroptosis, necroptosis, cuproptosis, and NETosis, have been observed to potentially reverse an immune desert-type tumor microenvironment and amplify anti-tumor immune responses.

Additionally, tertiary lymphoid structures (TLS) might play a positive role in anti-tumor process. One study illuminated that TLS abundance markedly increased in all advanced urothelial carcinoma patients with pathological complete response after immune checkpoint inhibitor (ICI) treatment. This suggests that ICIs can potentially induce TLS, bolstering localized anti-tumor immune responses. Furthermore, in melanoma patients treated with neoadjuvant ICIs, responders contained more abundant and diverse B cell receptor sequences as well as higher expression of B cell-specific genes. Moreover, TLS in melanoma tumor tissues responding to neoadjuvant anti-PD-1 therapy were enriched with a large number of reactive B cells which, in conjunction with other pivotal immune components of TLS, modified T cell activation and functionality.

The goal of this Research Topic is to establish a platform to advance research on the immune microenvironment of solid tumors to promote the mechanism explorations of immunotherapeutic sensitivity enhancement in the field of immune infiltration and programmed cell death as well as to improve translational medical applications and interventions in the attempt to optimize the outcomes of anti-tumor immunotherapy. We welcome submission of Original Research and Review articles including but not limited to:
1) Mechanism explorations of programmed cell death sensitizing anti-tumoral immunotherapy in solid tumors.
2) Mechanisms and signatures of immune infiltrations within the immune microenvironment of solid tumors on cancer immunotherapeutic sensitivity enhancements.
3) Tertiary lymphoid structures and anti-tumoral immune cell-epithelial cell interactions.
4) Cancer immunity atlas of solid tumors in single cell- and spatial- resolutions.
5) Human clinical trials using immune microenvironment-targeted anti-tumoral agents.
6) Combination studies - e.g. Immune checkpoint inhibitors + chemotherapeutic drugs.
7) Novel drug delivery systems with tumor immune microenvironment specificity.
8) Novel biomarkers for immunotherapeutic sensitivity grading or novel therapeutic approaches for anti-tumoral immunotherapy in microsatellite-stable solid 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: Immunotherapeutic Sensitivity, Immune Infiltration, Programmed Cell Death, Solid Tumor, Tumor Microenvironment

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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