Abstract
The presence of membranous immunopositivity of programmed death-ligand 1 (PD-L1) in tumors serves as a key determinant of response to immune checkpoint inhibitors. However, there are very limited studies on the evaluation of the PD-L1 mRNA expression and immunopositivity and their correlation with therapeutic response and survival outcomes, especially in Indian lung cancer patients. In this prospective study, conducted between 2017 and 2020, we collected biopsies and surgically resected tumors from 173 lung cancer patients. PD-L1 immunopositivity and mRNA expression were determined by immunohistochemistry using SP263 assay and qRT–PCR, respectively. PD-L1 expression was correlated with various clinicopathological variables, response to therapy, and survival outcomes using appropriate statistical methods. The median age was 60 years (range 33–81 years) with the majority of patients being male (86.5%) and smokers (83%). Histologically, the majority of patients were non-small cell lung cancer (89.4%) and of squamous cell carcinoma histology (64.3%). PD-L1 immunopositivity in tumor cells (tumor proportion score (TPS) ≥ 1%) was detected in 37.6%, while high immunopositivity (TPS ≥ 50%) was detected in 16.8% of lung cancer patients. Almost 76% of lung cancer patients with PD-L1 TPS ≥ 50% belonged to PD-L1 mRNA high-expression group. PD-L1 mRNA expression and immunopositivity did not correlate with response to therapy and survival outcomes. We conclude that PD-L1 immunopositivity and mRNA expression do not seem to serve as a prognostic biomarker for lung cancer patients treated with chemotherapy. More prospective studies should be planned to evaluate the predictive and prognostic relevance of PD-L1 expression in Indian lung cancer patients being treated with immune checkpoint inhibitors.
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Abbreviations
- NSCLC:
-
Non-small cell lung cancer
- SCLC:
-
Small cell lung cancer
- LUSC:
-
Lung squamous cell carcinoma
- LUAD:
-
Lung adenocarcinoma
- RNA:
-
Ribonucleic acid
- mRNA:
-
Messenger RNA
- rRNA:
-
Ribosomal RNA
- qRT–PCR:
-
Reverse transcription quantitative polymerase chain reaction
- OS:
-
Overall survival
- PFS:
-
Progression-free survival
- PD-1:
-
Programmed cell death protein 1
- PD-L1:
-
Programmed death-ligand 1
- ICIs:
-
Immune checkpoint inhibitors
- IHC:
-
Immunohistochemistry
- CT:
-
Computed tomography
- MRI:
-
Magnetic resonance imaging
- TPS:
-
Tumor proportion score
- RECIST:
-
Response evaluation criteria in solid tumors
- CR:
-
Complete response
- PR:
-
Partial response
- SD:
-
Stable disease
- PD:
-
Progressive disease
- CTCs:
-
Circulating tumor cells
- EGFR:
-
Epidermal growth factor receptor
- ALK:
-
Anaplastic lymphoma kinase
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Funding
This study is supported by an extramural research grant from Indian Council of Medical Research (ICMR), New Delhi (Grant No. 5/13/11/2019/NCD-III) and an intramural research grant from All India Institute of Medical Sciences, New Delhi (A-516).
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SK, MP, AM, IAM, and DJ performed laboratory experiments. SK and SKS performed data analysis. JS, PSM, SK, and AM provided clinical samples, and epidemiological and survival data. All the authors contributed significantly in the writing of the manuscript. All the authors read and approved the final manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by ethics committee of All India Institute of Medical Sciences, New Delhi (Ref. No. IEC-149/07.04.2017, RP-14/2017 and IEC-308/03.05.2019). This article does not contain any studies with animals performed by any of the authors.
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Kumar, S., Pandey, M., Mir, I.A. et al. Evaluation of the programmed death-ligand 1 mRNA expression and immunopositivity and their correlation with survival outcomes in Indian lung cancer patients. Human Cell 35, 286–298 (2022). https://doi.org/10.1007/s13577-021-00647-4
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DOI: https://doi.org/10.1007/s13577-021-00647-4