Prognostic value of PD-1, PD-L1 and PD-L2 deserves attention in head and neck cancer

Abstract

Head and neck cancer has high heterogeneity with poor prognosis, and emerging researches have been focusing on the prognostic markers of head and neck cancer. PD-L1 expression is an important basis for strategies of immunosuppressive treatment, but whether it has prognostic value is still controversial. Although meta-analysis on PD-L1 expression versus head and neck cancer prognosis has been performed, the conclusions are controversial. Since PD-L1 and PD-L2 are two receptors for PD-1, here we summarize and analyze the different prognostic values of PD-1, PD-L1, and PD-L2 in head and neck cancer in the context of different cell types, tissue localization and protein forms. We propose that for head and neck cancer, the risk warning value of PD-1/PD-L1 expression in precancerous lesions is worthy of attention, and the prognostic value of PD-L1 expression at different subcellular levels as well as the judgment convenience of prognostic value of PD-1, PD-L1, PD-L2 should be fully considered. The PD-L1 evaluation systems established based on immune checkpoint inhibitors (ICIs) are not fully suitable for the evaluation of PD-L1 prognosis in head and neck cancer. It is necessary to establish a new PD-L1 evaluation system based on the prognosis for further explorations. The prognostic value of PD-L1, PD-L2 expression in head and neck cancer may be different for early-stage and late-stage samples, and further stratification is required.

Circulating CD137+ T Cell Levels Are Correlated with Response to Pembrolizumab Treatment in Advanced Head and Neck Cancer Patients

“…To date, PD-L1 CPS is the most widely used biomarker for guiding the selection of (R/M) HNSCC patients for treatment based on predicted response, although with contradictory evidence. Its role as a biomarker has been demonstrated in different phase III clinical trials (KEYNOTE 040 and KEYNOTE 048) [ 7 , 39 ], in which it was observed that PD-L1 + patients showed increased survival. However, several other studies have shown similar therapeutic benefits for both PD-L1 + and PD-L1 − patients, with no significant difference in overall survival, suggesting that PD-L1 alone does not adequately distinguish which patients will benefit from treatment [ 40 , 41 ].…”

“…Most recently, pembrolizumab, an anti-PD1 antibody, was approved as an upfront treatment for HNSCC, completely changing the management of the affected patients. The phase III clinical trial Keynote 048 sanctioned the introduction of this agent as first-line treatment for patients with (R/M) HNSCC with a PD-L1 combined positive score (CPS) ≥1 [ 7 ]. Pembrolizumab, alone or in combination with platinum-based chemotherapy, significantly improves the overall survival (OS) of (R/M) HNSCC patients with CPS ≥1 or ≥20 compared with chemotherapy plus cetuximab, an anti-EGFR monoclonal antibody.…”

The Concordant Disruption of B7/CD28 Immune Regulators Predicts the Prognosis of Oral Carcinomas

“…Anti-PD-L1 therapy has been approved for neoadjuvant therapy of HNSCC and can improve the treatment outcomes, albeit with limited effects [ 3 ]. PD-L2 seems to be superior to PD-L1 in PD-1 binding [ 12 ], and it has been shown to be a prognostic factor of HNSCC in studies [ 26 , 27 ]. This study showed that the ratios of PD-L1 or PD-L2, normalized with ICOS and other CD28 members, also allowed for a good survival prediction for all cancers and HNSCC with nodal involvement in both cohorts using univariate modes.…”

“…Moreover, neoadjuvant anti-PD-1/PD-L1 immunotherapy may have advantages in operable HNSCC according to histopathological evaluation [ 25 ]. PD-L2 targeting-based immune annotations may serve as alternative markers to facilitate anti-PD-1 therapy [ 26 , 27 ]. Due to the pluripotent roles of CD276 in HNSCC pathogenesis, and since CD276 is a predictor for the responses to immunotherapy in HNSCC [ 20 ], the combined efficacies of anti-PD-1 and anti-CD276 targeting have been tested in advanced HNSCC [ 28 ].…”

Molecular basis, potential biomarkers, and future prospects of OSCC and PD-1/PD-L1 related immunotherapy methods

“…Studies have shown that in precancerous lesions such as actinic labyrinthitis [ 21 ] and oral leukoplakia [ 22 ], the expression of PD-1 and PD-L1 is up-regulated. The expression of PD-1 and PD-L1 in the epithelium (E) of the oral lichen planus (OLP) is different from that in the lower subepithelium (S), and the malignant transformation rate of tissues with elevated PD-L1 expression is significantly enhanced over a 5-year period [ 23 ].…”