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Published on: February 3, 2023
Correlation Between Programmed Death Receptor-1 Expression in Tumor-Infiltrating Lymphocytes and Programmed Death
Paloma Del C Monroig-Bosque, Brandon Driver, Joel A Morales-Rosado
1From the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Drs Monroig-Bosque, Deavers, Bernicker, Cagle, and Miller); the Department of Pathology, Weill Cornell Medicine, New York, New York (Drs Monroig-Bosque, Bernicker, Cagle, and Miller); the Department of Pathology, University of Arkansas for Medical Science, Little Rock (Dr Driver); the Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan (Dr Morales-Rosado); and Biocare Medical LLC, Pacheco, California (Dr Tacha).
Context.—:
The interaction between programmed death ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) on activated T cells sends an inhibitory signal that dampens the immune response. Tumors can express PD-L1 and evade the immune system. In advanced non-small cell lung carcinoma, expression of PD-1 in tumor-infiltrating lymphocytes (TILs) correlates with PD-L1 expression in tumor cells (TCs). However, this relationship has not been thoroughly explored in early disease.
Objective.—:
To investigate the correlation of PD-1 and PD-L1 in non-small cell lung carcinoma tumor samples, with emphasis on stage I disease.
Design.—:
Whole tissue sections from non-small cell lung carcinoma tumors were retrospectively evaluated by immunohistochemistry for PD-1 and PD-L1 expression. The scoring was based on the percentage of cells positive for PD-1 in TILs and PD-L1 in TCs and tumor-infiltrating immune cells (ICs).
Results.—:
Expression of PD-1 in TILs was observed in 147 of 161 non-small cell lung carcinoma cases (91%). The majority of cases negative for PD-1 also lacked PD-L1 in TCs. The 68 cases with highest PD-1 expression in TILs included 33 (49%) with expression of PD-L1 in TCs and ICs. Strong correlations were observed in patients with elevated PD-1 expression in TILs and PD-L1 in TCs ( P = .01) and ICs ( P = .003). Expression of PD-1 also correlated with increased PD-L1 in TCs and ICs when the 2 were grouped together ( P < .001). Finally, stage I patients with negative PD-1 and PD-L1 expression showed trends toward increased disease-specific survival.
Conclusions.—:
Expression of PD-1 in TILs correlates with PD-L1 expression in both TCs and ICs. Furthermore, negative expression of PD-1 and PD-L1 suggest trends toward disease-specific survival, even in early disease stages.
Insights
Programmed death receptor-1 (PD-1) expression in tumor-infiltrating lymphocytes correlates with programmed death ligand-1 (PD-L1) in tumor cells and immune cells in non-small cell lung carcinoma. Negative PD-1 and PD-L1 expression trends toward improved survival, even in early stages.
Area of Science:
- Immunology
- Oncology
- Pathology
Background:
- The programmed death receptor-1 (PD-1) and programmed death ligand-1 (PD-L1) pathway inhibits T cell-mediated immune responses.
- Tumors exploit the PD-1/PD-L1 interaction to evade immune surveillance.
- While PD-1/PD-L1 correlation is known in advanced non-small cell lung carcinoma (NSCLC), its role in early stages is less understood.
Purpose of the Study:
- To investigate the correlation between PD-1 and PD-L1 expression in non-small cell lung carcinoma (NSCLC) tumor samples.
- To specifically analyze this correlation in early-stage (Stage I) NSCLC.
Main Methods:
- Retrospective analysis of whole tissue sections from NSCLC tumors.
- Immunohistochemistry was used to evaluate PD-1 expression in tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in tumor cells (TCs) and immune cells (ICs).
- Scoring was based on the percentage of positive cells for PD-1 and PD-L1.
Main Results:
- PD-1 expression in TILs was detected in 91% of NSCLC cases.
- Strong correlations were found between elevated PD-1 in TILs and PD-L1 in TCs (P = .01) and ICs (P = .003).
- Negative PD-1 and PD-L1 expression showed a trend towards improved disease-specific survival in Stage I NSCLC patients.
Conclusions:
- PD-1 expression in TILs is significantly correlated with PD-L1 expression in both TCs and ICs in NSCLC.
- The absence of both PD-1 and PD-L1 expression may indicate a favorable prognosis, even in early disease stages.
- These findings highlight the potential of targeting the PD-1/PD-L1 axis in early-stage NSCLC.
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