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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

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Cellular dynamics of tumor microenvironment driving immunotherapy resistance in non-small-cell lung carcinoma

Shujie Huang1, Jeff Yat-Fai Chung1, Chunjie Li2

  • 1Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.

Cancer Letters
|September 26, 2024
PubMed

Insights

Immune checkpoint inhibitors (ICIs) show promise for non-small cell lung cancer (NSCLC), but resistance is common. Understanding the tumor microenvironment

Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Immune checkpoint inhibitors (ICIs) have revolutionized non-small cell lung cancer (NSCLC) treatment.
  • Primary and secondary resistance to ICIs present significant clinical challenges in advanced NSCLC.
  • The tumor microenvironment (TME) critically influences patient responses to immunotherapy.

Purpose of the Study:

  • To comprehensively review the interactive roles of immune and stromal cells within the TME in mediating ICI resistance in NSCLC.
  • To elucidate how diverse cellular interactions within the TME contribute to immunotherapy resistance.
  • To identify novel therapeutic targets and strategies for overcoming ICI resistance in NSCLC.

Main Methods:

  • Literature review synthesizing recent research on cellular interactions within the NSCLC TME.
  • Analysis of the dynamic interplay between T cells, B cells, neutrophils, macrophages, and cancer-associated fibroblasts (CAFs).
  • Exploration of mechanisms underlying T cell modulation by TME constituents.

Main Results:

  • The TME, comprising various immune and stromal cells, significantly impacts ICI efficacy.
  • Complex cellular interactions, including varying T cell states influenced by CAFs and other immune cells, drive resistance.
  • Understanding these interactions is key to predicting and overcoming treatment failure.

Conclusions:

  • The multifaceted mechanisms of ICI resistance in NSCLC are intricately linked to TME cellular crosstalk.
  • Targeting specific cellular interactions within the TME offers promising strategies to enhance ICI effectiveness.
  • This review provides insights for developing personalized treatment approaches to improve outcomes for NSCLC patients.
Keywords:
Clinical trialsImmunotherapy resistanceLung cancerT cellsTumor microenvironment

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