PD-L1 expression in human cancers and its association with clinical outcomes

Abstract

PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial. Blocking antibodies that target PD-1 and PD-L1 have achieved remarkable response rates in cancer patients who have PD-L1-overexpressing tumors. However, using PD-L1 as an exclusive predictive biomarker for cancer immunotherapy is questionable due to the low accuracy of PD-L1 immunohistochemistry staining. Factors that affect the accuracy of PD-L1 immunohistochemistry staining are as follows. First, antibodies used in different studies have different sensitivity. Second, in different studies, the cut-off value of PD-L1 staining positivity is different. Third, PD-L1 expression in tumors is not uniform, and sampling time and location may affect the results of PD-L1 staining. Therefore, better understanding of tumor microenvironment and use of other biomarkers such as gene marker and combined index are necessary to better identify patients who will benefit from PD-1/PD-L1 checkpoint blockade therapy.

Absence of PD-L1 on tumor cells is associated with reduced MHC I expression and PD-L1 expression increases in recurrent serous ovarian cancer

“…1D a Kaplan-Meier estimate is shown indicating a positive impact of the PD-L1 abundance (≥1% versus 0%) on overall survival (p = 0.045; Log-rank test), albeit supported by only few samples but in accordance to most evidences in ovarian cancer1617 which is in discordance to the impact of PD-L1 expression on survival in nearly all other cancer entities including gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, and bladder cancer18. The significant positive impact of PD-L1 expression holds also in a multiple Cox-regression analysis correcting individually for age (p = 0.049) and as a trend when correcting for residual tumor (p = 0.079).…”

PD-1/PD-L1 Blockade Therapy for Tumors with Downregulated MHC Class I Expression

“…In lung carcinoma, colorectal cancer, and melanoma, both worse and better prognoses were associated with PD-L1 expression. The inconsistency of the prognostic value of PD-L1 could stem from technical issues of the immunohistochemical (IHC) detection of PD-L1, and temporal and spatial factors that can be affected by the heterogeneity of PD-L1 expression in tumors [10]. …”

PD-1 Blockade Promotes Epitope Spreading in Anticancer CD8+ T Cell Responses by Preventing Fratricidal Death of Subdominant Clones To Relieve Immunodomination

“…B7-DC or CD273) (16, 17). PD-L1 is expressed, constitutively or inducibly, by a variety of hematopoietic and non-hematopoietic cells (10), and in various types of cancer (18). By contrast, PD-L2 has a much more restricted expression pattern and is primarily found on activated macrophages and myeloid dendritic cells (DCs) (10).…”