Immune Profiles and Immunotherapy Efficacy in Sinonasal Malignancies: A Scoping Review

Little is understood about the efficacy of immunotherapeutic strategies against sinonasal malignancies (SN) or their immunologic profiles. This review summarizes key immune markers within SN tumors and underscores known data on the efficacy of checkpoint inhibitors.

The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched from database inception to present to identify studies on SN malignancies, including SN squamous cell carcinoma (SNSCCa), adenocarcinoma (SNAC), undifferentiated carcinoma (SNUC), and olfactory neuroblastoma (ONB), their immune profiles, and immunotherapy efficacy.

Included studies were those that either investigated the tumor immune profile (cellular or molecular) or reported findings following the use of immune checkpoint inhibitors. Two separate teams of two reviewers performed dual, independent screening and full-text review of 675 studies, with 52 included in the final analysis.

Anti-programmed cell death protein-1 (PD-1) immunotherapy is the most investigated immune checkpoint inhibitor against SN malignancies. Checkpoint inhibitor efficacy showed the most promise for SNSCCa with comparatively few studies in SNAC, SNUC, and ONB. The prognostic value of tumor-infiltrating lymphocytes (TIL) density and programmed death ligand-1 (PD-L1) expression vary greatly between SN tumor subtypes. TILs, not PD-L1 expression, most consistently correlate with survival in SNSCCa, SNAC, and SNUC. ONBs are predominantly immune-cold.

SN tumor rarity and heterogeneity limits research in immunotherapy efficacy and prognostic biomarkers. Multi-institutional research endeavors aimed at evaluating both checkpoint inhibitor efficacy and the SN tumor immune microenvironment are essential in advancing SN tumor management.