Does ‘B’ stand for ‘benefit’? Decoding the B-cell neighborhood in head and neck cancer for predicting therapeutic response to PD-1 inhibitors

Programmed death receptor 1 (PD1) inhibitors are part of the standard treatment for patients with recurrent/ metastatic (R/M) head and neck squamous cell cancer (HNSCC). Although PD1 ligand Combined Positive Score (PDL1 CPS) expression is used routinely to select patients for PD1 inhibitors in the first-line setting, it’s predictive power is modest because even in the CPS > 20 subgroup from the KEYNOTE 048 study, the objective response rate (ORR) was just 19% with pembrolizumab alone [ 1 Burtness B. Harrington K.J. Greil R. et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019; 394: 1915-1928 Abstract Full Text Full Text PDF PubMed Scopus (1621) Google Scholar ]. Given the abundance of tumor infiltrating lymphocytes (TIL) in the tumor microenvironment (TME) of some HNSCCs, and the burgeoning literature on Tertiary Lymphoid Structures (TLS) in cancers, the limelight has now turned to the B-cell neighborhood. B-cell infiltration is associated with survival outcomes following programmed cell death protein 1 inhibition in head and neck squamous cell carcinomaAnnals of OncologyPreviewProgrammed cell death protein 1 (PD-1) axis blockade has become the mainstay in the treatment of recurrent and/or metastatic (R/M) head and neck squamous cell cancer (HNSCC). Programmed death-ligand 1 (PD-L1) is the only approved biomarker for patient selection; however, response rate is limited even among high expressors. Our primary objective was to investigate the association of immune cell-related biomarkers in the tumor and tumor microenvironment with PD-1 checkpoint inhibitors’ outcomes in patients with R/M HNSCC. Full-Text PDF Open Access