Biomarkers of response to PD-1/PD-L1 inhibition

Abstract

Immunotherapy is a promising treatment strategy for cancer that has recently shown unprecedented survival benefits in selected patients. A number of immunomodulatory agents that target immune system checkpoints such as the cytotoxic T-lymphocyte antigen 4 (CTLA-4), the programmed death-1 (PD-1) or its ligand (PD-L1), have received regulatory approval for the treatment of multiple cancers including malignant melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic head and neck squamous cell carcinoma. Nevertheless, a substantial proportion of patients treated with checkpoint inhibitors have little or no benefit while these treatments are costly and might have associated toxicities. Hence, the establishment of valid predictors of treatment response has become a priority. This review summarizes the current evidence around biomarkers of response to PD-1/PD-L1 inhibition, considering features related to the tumor and to the host immune system.

Association between pretreatment lymphocyte count and response to PD1 inhibitors in head and neck squamous cell carcinomas

“…In cancer types other than HNSCC, prior studies have shown that pretreatment lymphocyte counts as well as NLR are potential biomarkers associated with response to IO therapy [21, 22]. Several groups have observed that ALC and/or NLR are associated with response to IO therapy in melanoma patients [14, 23–25].…”

Inhibition of yes‐associated protein down‐regulates PD‐L1 (CD274) expression in human malignant pleural mesothelioma

“…Currently, tumour PD‐L1 expression is used as a predictive biomarker for immunotherapy targeting on the PD1/PD‐L1 axis 6. PD‐L1 appears to be expressed in a substantial proportion of human MPM 12, 24.…”

“…Immunotherapy targeting the immune checkpoint programmed death‐1 (PD‐1)/PD‐ligand (L) 1 axis has been used to treat various cancers including non‐small‐cell lung cancer, melanoma, renal cell carcinoma and Hodgkin lymphoma 6, 7, 8, 9, 10. Recently, PD‐1/PD‐L1 inhibitors were also used to treat patients with advanced MPM, and several clinical trials are ongoing 11, 12.…”

“…Recently, PD‐1/PD‐L1 inhibitors were also used to treat patients with advanced MPM, and several clinical trials are ongoing 11, 12. Tumour PD‐L1 expression has been used as a predictive biomarker for PD‐1/PD‐L1 inhibitors 6, 12, 13. However, how the tumour PD‐L1 expression is regulated in cancer cells is not obvious.…”

High IDO1 Expression Is Associated with Poor Outcome in Patients with Anal Cancer Treated with Definitive Chemoradiotherapy

“…Predicting which patients will respond to immune checkpoint therapy is challenging. Although PD‐L1 expression has been associated with anti‐PD‐1/PD‐L1 response in a variety of settings, several studies have shown a lack of association between PD‐L1 expression and response to PD‐1 inhibition . A variety of other markers are under investigation.…”