J Pathol Transl Med.  2021 Nov;55(6):398-405. 10.4132/jptm.2021.08.08.

Programmed death-ligand 1 expression and tumor-infiltrating lymphocytes in non-small cell lung cancer: association with clinicopathologic parameters

Affiliations
  • 1Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  • 2Department of Pulmonary and Critical Care Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Abstract

Background
Data on the prevalence of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in non–small cell lung cancer (NSCLC) and their clinical significance in Indian patients are limited.
Methods
Newly diagnosed NSCLC cases (adenocarcinoma or squamous cell carcinoma [SqCC] histology) were included in the present study. The TILs were evaluated based on morphology on hematoxylin and eosin–stained slides. PD-L1 expression in tumors was assessed using immunohistochemistry with rabbit monoclonal antibody (SP263) on the Ventana automated immunostainer. Tumors with PD-L1 expression > 50% on tumor cells were considered PD-L1–positive. Tumors in which TILs occupy > 25% of stroma were considered to have high TILs. The association of PD-L1 expression and TILs with various clinical parameters including overall survival (OS) was investigated.
Results
The present study included 128 cases of NSCLC (67 adenocarcinoma, 61 SqCC). PD-L1 positivity was observed in 17.2% of the patients with NSCLC. Baseline characteristics of PD-L1–positive subjects were similar to PD-L1–negative subjects except for a higher prevalence of liver metastasis (18.2% vs. 2.8%; p = .018) and a higher probability of diagnosis from extrapulmonary biopsies. High TILs were observed in 26.6% of the subjects. However, PD-L1 expression and high TIL did not affect OS.
Conclusions
PD-L1 positivity and high TILs were observed in 20% and 25% of the patients with NSCLC, respectively, however, neither were predictors of survival in SqCC.

Keyword

Lung neoplasms; Non-small cell lung carcinoma; PD-L1; Immunotherapy; Tumor-infiltrating lymphocytes

Figure

  • Fig. 1 Photomicrographs (programmed death-ligand 1 [PD-L1] staining using SP263 clone) showing positive control (PD-L1 staining in placenta) (A), TC2 (PD-L1 expression on > 50% of tumor cells [TCs]) (B), TC1 (PD-L1 expression on 1%–50% TCs) (C), and TC0 (PD-L1 expression on < 1% of TCs) (D).

  • Fig. 2 Photomicrographs (× 200) of hematoxylin and eosin staining showing TIL0 (0%–5% of tumor stroma occupied by tumor-infiltrating lymphocytes [TILs]) (A), TIL3 (> 50% of tumor stroma occupied by TILs) (B).

  • Fig. 3 Kaplan-Meir plots for overall survival (OS). OS of programmed death-ligand 1 (PD-L1)–positive subjects was not different from PD-L1–negative subjects. The median (95% confidence interval) OS was 7.6 months (6.5–8.8) in subjects who were PDL1–negative compared with 8.5 months (1.1–16.0) in subjects who were PD-L1-positive (log-rank p = .584).


Reference

References

1. Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019; 393:1819–30.
2. Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018; 378:2288–301.
Article
3. Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018; 378:2078–92.
Article
4. Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018; 379:2040–51.
Article
5. Zhang M, Li G, Wang Y, et al. PD-L1 expression in lung cancer and its correlation with driver mutations: a meta-analysis. Sci Rep. 2017; 7:10255.
Article
6. Dietel M, Savelov N, Salanova R, et al. Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non-small-cell lung cancer: the global, multicenter EXPRESS study. Lung Cancer. 2019; 134:174–9.
Article
7. Vallonthaiel AG, Malik PS, Singh V, et al. Clinicopathologic correlation of programmed death ligand-1 expression in non-small cell lung carcinomas: a report from India. Ann Diagn Pathol. 2017; 31:56–61.
Article
8. Kumar M, Guleria B, Swamy S, Soni S. Correlation of programmed death-ligand 1 expression with gene expression and clinicopathological parameters in Indian patients with non-small cell lung cancer. Lung India. 2020; 37:145–50.
Article
9. Brambilla E, Le Teuff G, Marguet S, et al. Prognostic effect of tumor lymphocytic infiltration in resectable non-small-cell lung cancer. J Clin Oncol. 2016; 34:1223–30.
Article
10. Bremnes RM, Busund LT, Kilvaer TL, et al. The role of tumor-infiltrating lymphocytes in development, progression, and prognosis of non-small cell lung cancer. J Thorac Oncol. 2016; 11:789–800.
Article
11. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015; 10:1243–60.
12. Hendry S, Salgado R, Gevaert T, et al. Assessing tumor-infiltrating lymphocytes in solid tumors: a practical review for pathologists and proposal for a standardized method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in melanoma, gastrointestinal tract carcinomas, non-small cell lung carcinoma and mesothelioma, endometrial and ovarian carcinomas, squamous cell carcinoma of the head and neck, genitourinary carcinomas, and primary brain tumors. Adv Anat Pathol. 2017; 24:311–35.
Article
13. Bal A, Singh N, Agarwal P, Das A, Behera D. ALK gene rearranged lung adenocarcinomas: molecular genetics and morphology in cohort of patients from North India. APMIS. 2016; 124:832–8.
14. Prasad KT, Kaur H, Muthu V, Aggarwal AN, Behera D, Singh N. Interconversion of two commonly used performance tools: an analysis of 5844 paired assessments in 1501 lung cancer patients. World J Clin Oncol. 2018; 9:140–7.
Article
15. Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007; 2:706–14.
Article
16. Singh N, Aggarwal AN, Behera D. Management of advanced lung cancer in resource-constrained settings: a perspective from India. Expert Rev Anticancer Ther. 2012; 12:1479–95.
Article
17. Prasad KT, Muthu V, Biswas B, et al. Utility and safety of maintenance chemotherapy in advanced non-small cell lung cancer across various performance status categories: real-world experience. Curr Probl Cancer. 2020; 44:100565.
Article
18. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92:205–16.
19. Garg A, Batra U, Choudhary P, et al. Clinical predictors of response to EGFR-tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer: a real-world multicentric cohort analysis from India. Curr Probl Cancer. 2020; 44:100570.
20. Patel A, Batra U, Prasad KT, et al. Real world experience of treatment and outcome in ALK-rearranged metastatic nonsmall cell lung cancer: a multicenter study from India. Curr Probl Cancer. 2020; 44:100571.
21. McLaughlin J, Han G, Schalper KA, et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol. 2016; 2:46–54.
Article
22. Sorensen SF, Zhou W, Dolled-Filhart M, et al. PD-L1 expression and survival among patients with advanced non-small cell lung cancer treated with chemotherapy. Transl Oncol. 2016; 9:64–9.
Article
23. Calles A, Liao X, Sholl LM, et al. Expression of PD-1 and its ligands, PD-L1 and PD-L2, in smokers and never smokers with KRAS-mutant lung cancer. J Thorac Oncol. 2015; 10:1726–35.
24. Hirsch FR, McElhinny A, Stanforth D, et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project. J Thorac Oncol. 2017; 12:208–22.
Article
25. Parra ER, Villalobos P, Mino B, Rodriguez-Canales J. Comparison of different antibody clones for immunohistochemistry detection of programmed cell death ligand 1 (PD-L1) on non-small cell lung carcinoma. Appl Immunohistochem Mol Morphol. 2018; 26:83–93.
Article
26. Kim H, Kwon HJ, Park SY, Park E, Chung JH. PD-L1 immunohistochemical assays for assessment of therapeutic strategies involving immune checkpoint inhibitors in non-small cell lung cancer: a comparative study. Oncotarget. 2017; 8:98524–32.
Article
27. Mandarano M, Bellezza G, Belladonna ML, et al. Assessment of TILs, IDO-1, and PD-L1 in resected non-small cell lung cancer: an immunohistochemical study with clinicopathological and prognostic implications. Virchows Arch. 2019; 474:159–68.
Article
28. He Y, Rozeboom L, Rivard CJ, et al. PD-1, PD-L1 protein expression in non-small cell lung cancer and their relationship with tumor-infiltrating lymphocytes. Med Sci Monit. 2017; 23:1208–16.
Article
29. Geng Y, Shao Y, He W, et al. Prognostic role of tumor-infiltrating lymphocytes in lung cancer: a meta-analysis. Cell Physiol Biochem. 2015; 37:1560–71.
Article
30. Muthu V, Bal A, Gupta N, Prasad K, Behera D, Singh N. P2.03-053 A five-year audit of EGFR and ALK testing at a tertiary care centre in North India: more sensitive methods do make a difference! J Thorac Oncol. 2017; 12:S2395.
Article
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