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<p>Beyond cancer cells, the tumor microenvironment (TME) includes cells of the innate and adaptive immune systems but also non-immune cells, such as fibroblasts and endothelial cells. Depending on the cues they receive, infiltrating myeloid cells, such as monocytes, macrophages, dendritic cells and neutrophils, perform immune stimulatory or suppressive functions by educating adaptive immune cells, thereby guiding their responses to cancer cells and cancer treatment, such as immune checkpoint blockade (ICB). The increasing understanding that anti-tumor immunity goes beyond T cells with improved functionality, and the unraveling of resistance mechanisms beyond T cell exhaustion, have renewed interest in non-T cell components of the TME to identify novel therapeutic targets and improve ICB responses. Here, we review immune and non-immune cellular components of the TME that regulate adaptive cell responses and their role in ICB response and resistance.</p>

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The tumor microenvironment’s role in the response to immune checkpoint blockade

  • 期刊论文

  • 发表日期：

    2025年6月13日

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  • Konstantinos Aliazis,
  • Anthos Christofides,
  • Rushil Shah,
  • Yao Yu Yeo,
  • Sizun Jiang,
  • Alain Charest,
  • Vassiliki A. Boussiotis

摘要

Beyond cancer cells, the tumor microenvironment (TME) includes cells of the innate and adaptive immune systems but also non-immune cells, such as fibroblasts and endothelial cells. Depending on the cues they receive, infiltrating myeloid cells, such as monocytes, macrophages, dendritic cells and neutrophils, perform immune stimulatory or suppressive functions by educating adaptive immune cells, thereby guiding their responses to cancer cells and cancer treatment, such as immune checkpoint blockade (ICB). The increasing understanding that anti-tumor immunity goes beyond T cells with improved functionality, and the unraveling of resistance mechanisms beyond T cell exhaustion, have renewed interest in non-T cell components of the TME to identify novel therapeutic targets and improve ICB responses. Here, we review immune and non-immune cellular components of the TME that regulate adaptive cell responses and their role in ICB response and resistance.