Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell Death Protein-1 Targeting and Differential Expression of Immunological Markers: A Case Report
Authors: Maysaloun Merhi, Afsheen Raza, Varghese Philipose Inchakalody, Abdulqadir Jeprel Japer Nashwan, Niloofar Allahverdi, Roopesh Krishnankutty, Shahab Uddin, Abdul Rehman Zar Gul, Mohammed Ussama Al Homsi, Said Dermime
Journal: Front Immunol (2018)
Keywords: ny-eso-1 antibody, ny-eso-1-specific t cells, cytokine profile, head and neck squamous cell carcinoma, nivolumab, programmed cell death protein-1
MeSH terms: Antineoplastic Agents, Immunological / therapeutic use, Carcinoma, Squamous Cell / drug therapy, Carcinoma, Squamous Cell / immunology, Gene Expression Regulation, Neoplastic / drug effects, Head and Neck Neoplasms / drug therapy, Head and Neck Neoplasms / immunology, Programmed Cell Death 1 Receptor / antagonists & inhibitors, Case Reports, Research Support, Non-U.S. Gov't, Aged, Antineoplastic Agents, Immunological / pharmacology, Biomarkers, Tumor, Carcinoma, Squamous Cell / diagnosis, Carcinoma, Squamous Cell / metabolism, Cytokines / blood, Head and Neck Neoplasms / diagnosis, Head and Neck Neoplasms / metabolism, Humans, Immunomodulation / drug effects, Male, Nivolumab / pharmacology, Nivolumab / therapeutic use, Positron Emission Tomography Computed Tomography, Programmed Cell Death 1 Receptor / genetics, Tomography, X-Ray Computed, Treatment Outcome, Antineoplastic Agents, Immunological, Biomarkers, Tumor, Cytokines, Programmed Cell Death 1 Receptor, Nivolumab

Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway has been shown to enhance T cell-mediated antitumor immunity. Clinical responses are limited to subgroups of patients. The search for biomarkers of response is a strategy to predict response and outcome of PD-1/PD-L1 checkpoint intervention. The NY-ESO-1 cancer testis antigen has been considered as a biomarker in head and neck squamous cell carcinoma (HNSCC) patients and can induce both specific NY-ESO-1 antibody and T cells responses. Here, we correlated clinical responsiveness to anti-PD-1 (nivolumab) treatment with immunity to NY-ESO-1 in a patient with recurrent HNSCC. The patient was treated with second-line treatment of nivolumab and had a stable disease for over 7 months. His NY-ESO-1 antibody was found to be lower after the third (****p < 0.0001) and the fifth (****p < 0.0001) cycles of treatment compared to base line, and this was in line with the stability of the disease. The NY-ESO-1-specific T cells response of the patient was found to be increased after the third and the fifth (**p = 0.002) cycles of treatment but had a significant decline after progression (**p = 0.0028). The PD-1 expression by the patient's T cells was reduced 15-folds after nivolumab treatment and was uniquely restricted to the CD8+ T cells population. Several cytokines/chemokines involved in immune activation were upregulated after nivolumab treatment; two biomarkers were reduced at progression [interleukin (IL)-10: ****p < 0.0001 and CX3CL1: ****p < 0.0001]. On the other hand, some cytokines/chemokines contributing to immune inhibition were downregulated after nivolumab treatment; two biomarkers were increased at progression (IL-6: ****p < 0.0001 and IL-8: ****p < 0.0001). This data support the notion that the presence of anti-NY-ESO-1 integrated immunity and some cytokines/chemokines profile may potentially identify a response to PD-1 blockade in HNSCC patients.