Spatial Architecture and Temporal Dynamics of Tumor Microenvironment: Implications in Tumor Immunity and Immunotherapies

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Background

Cancers are complex and dynamic entities constantly reshaped by the interactions between neoplastic cells and their microenvironments. Immunotherapies have revolutionized the paradigm of cancer treatment, although only a subset of patients can benefit from durable responses. Cellular components in the TME, such as T cells, macrophages, and fibroblasts, are proven to be highly heterogeneous and will influence both disease progression and therapeutic responses.

The cellular components in the TME organize in spatially structured arrangements. The position of any given cell, relative to its neighbors and non-cellular structures, can provide helpful information for defining cellular phenotype, cell state, and ultimately cell and tissue function. Thus, not only the cellular compositions of the TME but also the spatial architecture and spatially resolved cell-cell crosstalk in tissue context will impact tumor control and progression, as well as the efficacy of immunotherapies.

Emerging evidence indicates that the cellular components within the tumor microenvironment (TME) exhibit dramatic heterogeneity, and various cellular states have been identified, particularly with advances in single-cell technologies. Single-cell technologies, especially scRNA-seq, have been utilized to characterize the TME at an unprecedented depth and revealed vast cellular diversity. Until recently, however, these high-throughput techniques could not be applied in situ, resulting in the loss of information about spatial relationships among the cataloged cell populations. The spatial distributions and regulatory mechanisms of these subtypes within TME, as well as their influences on disease progression and therapeutic responses, remain elusive.

Spatially resolved transcriptomics (SRT) has recently emerged as a technique capable of capturing the positional context of transcriptional activity within intact tissue. By preserving tissue architecture, SRT provides valuable insights into the spatial organization of cellular components and gene expression patterns.

This Research Topic provides a platform for gathering innovative studies that investigate the spatial compositions and organizations of the TME in different conditions across various cancer types. We aim to advance research on the spatial architecture, cellular crosstalk, and temporal dynamics of the TME to enhance our comprehension of their significance in tumor progression and immunotherapies. Our objective is to contribute to the advancement of knowledge in the field of tumor immunology and immunotherapies, which can potentially have a profound impact on improving patient outcomes and revolutionizing cancer therapeutics.

We welcome submissions of Original Research and Review articles focusing on but not limited to:
1) Spatially resolved cell-cell interactions or crosstalk within the TME;
2) Intra- and inter-tumor heterogeneities in cellular compositions and spatial architectures within the TME;
3) Spatial evolution of the TME structure during tumor progression;
4) Differences in cellular compositions and spatial architecture of the TME between primary tumors, recurrent tumors, or metastatic tumors;
5) Subtype- or cancer type-specific TME in terms of cellular compositions or spatial architectures;
6) The mechanisms of T cell activation and dysfunction within the spatial context of the TME;
7) The spatial organization and cellular neighborhoods of different subtypes of immune cells or stromal cells within the TME;
8) The spatial cellular and molecular heterogeneity of Tertiary Lymphoid Structures (TLS) within the TME, or the underlying mechanisms of T-B cell interactions within TLS;
9) The spatial architecture of the TME and its relationship with clinical variables;
10) The dynamics of cellular composition or spatial architecture within the TME following immunotherapies or combination therapies, such as immune checkpoint inhibitors in combination with chemotherapies.

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: Spatial Architecture, Temporal Dynamics, Tumor Microenvironment, Tumor Immunity, Immunotherapy

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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