Expression of PD-L1 Identifies a Subgroup of More Aggressive Non-Small Cell Carcinomas of the Lung

Abstract

Objectives: In light of various trials showing impressive response rates when treating non-small cell lung cancer (NSCLC) patients with anti PD-1/PD-L1 antibodies, the currently equivocal role of PD-L1 expression in NSCLC is in need of further clarification. Methods: We therefore analyzed the expression of PD-L1 on 293 well-documented NSCLC cases and correlated the results with clinical, histopathological and immunohistochemical characteristics. Results: The expression of PD-L1 on NSCLC was a poor prognostic factor for patients with nodal-negative adenocarcinoma (ACA) and, independent of other covariates, in tumors with increased CD8+ tumor-infiltrating lymphocytes (TILs). Expression of PD-L1 was more commonly seen in ACA and in male patients with a past and current smoking history. Finally, PD-L1+ TILs were more often found in squamous and large cell carcinomas. Conclusions: Should the expression of PD-L1 be on the verge of becoming an additional biomarker for routine diagnostics in NSCLC, our findings will provide important further insight and could contribute towards more effectively stratifying patients. These results may single out certain patient groups with a potential for increased benefit from anti PD-1/PD-L1 treatment strategies and should be considered in future trials.

Expression of PD‐L1 correlates with pleomorphic morphology and histological patterns of non‐small‐cell lung carcinomas

“…It is also noticeable that the extent of staining increases from those tumours that are lepidic‐predominant to those that are acinar/papillary‐predominant to those are solid/micropapillary‐predominant. This result is in agreement with other studies showing that solid components of ADCs have high PD‐L1 expression . Our data also correlate with several studies on the importance of a predominant pattern for prognostication in resected ADCs, and, should a grading system based on a predominant pattern and pleomorphic features be implemented, this might have predictive value in relation to the response to immunomodulatory therapy, in similar fashion to solid/micropapillary patterns having relevance in relation to the response to conventional chemotherapy in an adjuvant setting …”

“…This result is in agreement with other studies showing that solid components of ADCs have high PD-L1 expression. [33][34][35][36][37] Our data also correlate with several studies on the importance of a predominant pattern for prognostication in resected ADCs, [16][17][18][19][20][21]36,38 and, should a grading system based on a predominant pattern and pleomorphic features be implemented, this might have predictive value in relation to the response to immunomodulatory therapy, in similar fashion to solid/micropapillary patterns having relevance in relation to the response to conventional chemotherapy in an adjuvant setting. 39 Indeed, analysis of those cases that have any lepidic component raises a further issue in relation to the variable nature of PD-L1 staining.…”

“…Non‐small‐cell lung carcinomas with particular architectural components have a worse prognosis, and our study has shown that these tumours are associated with high PD‐L1 expression. There is some evidence that PD‐L1 expression is related to the escape of host immune surveillance, and that higher PD‐L1 expression in NSCLC is associated with a worse prognosis . We postulate that NSCLCs with poor prognostic architectural patterns have improved mechanisms for escaping host immune surveillance.…”

“…There is some evidence that PD-L1 expression is related to the escape of host immune surveillance, and that higher PD-L1 expression in NSCLC is associated with a worse prognosis. 33,41 We postulate that NSCLCs with poor prognostic architectural patterns have improved mechanisms for escaping host immune surveillance. This may partly explain the worse prognosis of pleomorphic carcinoma 24 and solid-predominant NSCLC.…”

PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer

“…Therefore, tumor microenvironment-based biomarkers might be more valuable in predicting GC prognosis. PD-L1 and PD-L2 are expressed not only in the tumor cells (TCs), but also in the tumor-infiltrating immune cells (TIICs) [ 12 , 13 ]. Patients with positive PD-L1 expression in the TIICs have a greater response to anti-PD-1/PD-L1 treatment.…”