Circulating T Cell Subpopulations Correlate With Immune Responses at the Tumor Site and Clinical Response to PD1
Nataly Manjarrez-Orduño1, Laurence C Menard1, Selena Kansal1
1Bristol-Myers Squibb, Princeton, NJ, United States.
Abstract:
Agents targeting the PD1-PDL1 axis have transformed cancer therapy. Factors that influence clinical response to PD1-PDL1 inhibitors include tumor mutational burden, immune infiltration of the tumor, and local PDL1 expression. To identify peripheral correlates of the anti-tumor immune response in the absence of checkpoint blockade, we performed a retrospective study of circulating T cell subpopulations and matched tumor gene expression in melanoma and non-small cell lung cancer (NSCLC) patients. Notably, both melanoma and NSCLC patients whose tumors exhibited increased inflammatory gene transcripts presented high CD4+ and CD8+ central memory T cell (CM) to effector T cell (Eff) ratios in blood. Consequently, we evaluated CM/Eff T cell ratios in a second cohort of NSCLC. The data showed that high CM/Eff T cell ratios correlated with increased tumor PDL1 expression. Furthermore, of the 22 patients within this NSCLC cohort who received nivolumab, those with high CM/Eff T cell ratios, had longer progression-free survival (PFS) (median survival: 91 vs. 215 days). These findings show that by providing a window into the state of the immune system, peripheral T cell subpopulations inform about the state of the anti-tumor immune response and identify potential blood biomarkers of clinical response to checkpoint inhibitors in melanoma and NSCLC.
Insights
Peripheral T cell ratios can predict response to cancer immunotherapy. High central memory (CM) to effector (Eff) T cell ratios in blood correlate with better progression-free survival (PFS) in NSCLC patients treated with PD1-PDL1 inhibitors.
Area of Science:
- Immunology
- Oncology
- Translational Medicine
Background:
- PD1-PDL1 inhibitors have revolutionized cancer therapy.
- Clinical response to these agents depends on tumor mutational burden, immune infiltration, and PDL1 expression.
- Peripheral correlates of anti-tumor immunity are needed to guide treatment decisions.
Purpose of the Study:
- To identify peripheral blood biomarkers of anti-tumor immune response.
- To investigate the relationship between circulating T cell subpopulations and tumor characteristics.
- To assess the predictive value of T cell ratios for clinical response to checkpoint inhibitors.
Main Methods:
- Retrospective analysis of circulating T cell subpopulations and tumor gene expression in melanoma and NSCLC patients.
- Evaluation of CD4+ and CD8+ central memory (CM) to effector (Eff) T cell ratios.
- Correlation analysis with tumor PDL1 expression and clinical outcomes, including progression-free survival (PFS).
Main Results:
- High CM/Eff T cell ratios in blood were associated with increased inflammatory gene transcripts in tumors for both melanoma and NSCLC.
- In a NSCLC cohort, high CM/Eff T cell ratios correlated with increased tumor PDL1 expression.
- NSCLC patients with high CM/Eff T cell ratios receiving nivolumab showed significantly longer PFS (median 215 vs. 91 days).
Conclusions:
- Peripheral T cell subpopulations, specifically CM/Eff ratios, reflect the anti-tumor immune response.
- These T cell ratios may serve as blood biomarkers to predict clinical response to PD1-PDL1 inhibitors in melanoma and NSCLC.
- This study highlights the potential of peripheral immune monitoring in guiding cancer immunotherapy.
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