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Cancer

Resistance to Anti-PD-1 Therapy in Cancer Reveals New Mechanisms

Strategic Insights

— 2 min read

Research conducted by a team of scientists at Zhejiang University School of Medicine has shed new light on the mechanisms behind resistance to anti-PD-1 therapy in non-small cell lung cancer (NSCLC). The study, published in the Journal for ImmunoTherapy of Cancer, found that galectin-9 expressing tumor cells play a crucial role in sustaining primary resistance to neoadjuvant anti-PD-1 therapy.

The researchers used a multi-omics approach, including mass cytometry, single-cell RNA-seq, bulk RNA-seq, and polychromatic flow cytometry, to analyze tumor samples from NSCLC patients who received neoadjuvant anti-PD-1 therapy. Their findings revealed a correlation between the quantity and differentiation status of tissue-resident memory CD8+ T cells (CD8+ TRMs) and therapeutic efficacy. In contrast, the quantity of immature CD1c+ classical type 2 dendritic cells (imcDC2) and galectin-9+ cancer cells was negatively correlated with therapeutic efficacy.

The study also identified an epithelium/imDC2 suppressive axis that restrains the antitumor response of CD8+ TRMs via galectin-9/TIM-3. Furthermore, the expression level of CD8+ TRMs and galectin-9+ cancer cell-related genes predicted the clinical outcome of anti-PD-1 neoadjuvant therapy in human NSCLC patients.

Key Takeaways:

  • Galectin-9 expressing tumor cells sustain primary resistance to neoadjuvant anti-PD-1 therapy in NSCLC through galectin-9/TIM-3-mediated suppression of imcDC2 and CD8+ TRMs.
  • Supplementing anti-TIM-3 can break the epithelium/imcDC2/CD8+ TRMs suppressive loop to overcome anti-PD-1 resistance.
  • The quantity and differentiation status of CD8+ TRMs are positively correlated with therapeutic efficacy of neoadjuvant anti-PD-1 therapy in human NSCLC.
  • The quantity of immature CD1c+ classical type 2 dendritic cells (imcDC2) and galectin-9+ cancer cells is negatively correlated with therapeutic efficacy.
  • An epithelium/imDC2 suppressive axis restrains the antitumor response of CD8+ TRMs via galectin-9/TIM-3.
  • The expression level of CD8+ TRMs and galectin-9+ cancer cell-related genes predict the clinical outcome of anti-PD-1 neoadjuvant therapy in human NSCLC patients.

Statistics:

  • 12(8) - The issue number of the Journal for ImmunoTherapy of Cancer where the study was published.
  • 2024 - The year in which the study was published.
  • NCT03732664 - The trial registration number for the study.
  • 10.1136/jitc-2023-007854 - The DOI for the study.
  • 6451 - The page number where the study was reported in Health & Medicine Week.

Sources:

  • Journal for ImmunoTherapy of Cancer. (2024,12(8)). Epithelium/imcDC2 axis facilitates the resistance of neoadjuvant anti-PD-1 in human NSCLC.
  • NewsRx. (2024, August 30). Studies from Zhejiang University School of Medicine Describe New Findings in Cancer (Epithelium/imcDC2 axis facilitates the resistance of neoadjuvant anti-PD-1 in human NSCLC). Health & Medicine Week. p 6451.

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