Community Series in Implications of Immune Landscape in Tumor Microenvironment: Volume II

This Research Topic is the second volume of the “Implications of Immune Landscape in Tumor Microenvironment” Community Series. Please see Volume I here

Tumor microenvironment (TME) plays an important role in immunosuppressive mechanisms that result in immune editing and treatment resistance. Elucidating the diversity of stromal and immune cell distribution, polarization, and changes in their gene expression signatures will enable a better understanding of key events to improve treatment and prognosis. With the onset of immune checkpoint inhibitors (ICIs) in clinics for patients with solid tumors and hematologic malignancies, immunotherapy has taken a new direction in cancer management, especially as combination therapies. However, limitations encountered with the use of ICIs, including toxicity and immune-related adverse events (irAE) indicate the need to understand multiple regulatory mechanisms at both cellular and molecular levels that alter the immune landscape of the TME. Since predominant changes in the immune landscape occur at the TME, focussed deliberation on these events will provide a comprehensive understanding on this topic for scientists in the fields of basic, translational, and clinical cancer immunology.

The heterogeneity of TME and complex immune landscape pose major challenges in the treatment of solid tumors. Thus, integrative approaches, which relate immune mechanisms in the TME to that of peripheral and systemic immune signatures are essential to improve our understanding of the disease complexity and possibly improve immunotherapy outcomes. Such multiparametric studies should combine advances in current understanding of cancer immunobiology with powerful technologies, such as single-cell and spatial transcriptomics, and high dimensional flow cytometry that rapidly expand our ability to explore these interactions. Notably, tumor heterogeneity and inflammatory mediators in the TME vary significantly in neoplasms based on mutational load, lymphocyte infiltration, expression of checkpoint molecules, soluble inhibitors, and tumor cell metabolism. Overall, connecting key events to immune signatures that conform to a consensus will provide a benchmark to delve further into this important topic. Other parameters such as myeloid and lymphoid cell polarization to alter the immune homeostasis at the TME, favoring a tumor-supportive milieu would provide a macroscopic picture that may help guide treatment choices for more refined personalized tumor immunotherapy.

We welcome the submission of Original Research articles, Reviews, Perspectives, and Opinion articles focusing on the following areas:

• Mutations that dictate the immunologic landscape and response to immune checkpoint therapy
• Spatial immune landscape in the tumor-immune microenvironment
• Cellular mechanisms of tumor immune escape
• Implications of senescence in cancer immunotherapy
• Epigenetic mechanisms regulating changes in immune landscape and master regulators of cancer immune checkpoints
• Predictive and prognostic implications of tumor-immune and stromal signatures
• Extracellular vesicles modulating the tumor-immune microenvironment
• Targeting immunosuppressive cells such as regulatory T cells and MDSCs for cancer immunotherapy
• Next generation technologies to decipher tumor microenvironment.


Please note that 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 scope for this section and will not be accepted as part of this Research Topic.