Intratumoral CD39⁺CD8⁺ T Cells Predict Response to Programmed Cell Death Protein-1 or Programmed Death Ligand-1...

Area of Science:

• Oncology
• Immunology
• Biomarker Discovery

Background:

• Programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade is a key treatment for metastatic non-small cell lung cancer (NSCLC).
• Clinical response to PD-1/PD-L1 inhibitors varies, necessitating improved biomarkers for predicting treatment outcomes.
• CD39+CD8+ immune cells have been identified as tumor antigen-specific, cytotoxic T cells in treatment-naive NSCLC.

Purpose of the Study:

• To evaluate the clinical relevance of quantifying CD39+CD8+ T cells as a predictive biomarker for immunotherapy response in NSCLC.
• To compare the accuracy of multiplex immunohistochemistry (mIHC) with other methods for measuring CD39+CD8+ T cells.

Main Methods:

• Compared cytometry by time-of-flight (CyTOF) data with conventional immunohistochemistry (IHC), multiplex IHC (mIHC), and NanoString gene expression assays.
• Assessed the specificity and sensitivity of mIHC in a retrospective NSCLC cohort.
• Correlated CD39+CD8+ T cell proportion measured by mIHC with clinical response to PD-1/PD-L1 inhibitors.

Main Results:

• Multiplex IHC (mIHC) quantification of CD39+CD8+ T cells correlated with CyTOF results.
• The CD39+CD8+ T cell proportion determined by mIHC successfully stratified responders (63.6% ORR) from non-responders (0% ORR) to PD-1/PD-L1 inhibitors.
• This predictive capability was independent of other clinical and pathological factors, including PD-L1 status and EGFR mutation.

Conclusions:

• Multiplex IHC is a clinically relevant method for quantifying CD39+CD8+ T cells in NSCLC.
• CD39+CD8+ T cell proportion measured by mIHC shows potential as a predictive biomarker for immunotherapy response in NSCLC.
• Further validation in additional cohorts is warranted to confirm the utility of this biomarker.