Increased PD-1 + and TIM-3 + TILs during Cetuximab Therapy Inversely Correlate with Response in Head and Neck Cancer Patients

• Published in: Cancer immunology research Vol. 5; no. 5; p. 408
• Main Authors: Jie, Hyun-Bae, Srivastava, Raghvendra M, Argiris, Athanassios, Bauman, Julie E, Kane, Lawrence P, Ferris, Robert L
• Format: Journal Article
• Language: English
• Published: United States 01.05.2017
• Subjects: Antineoplastic Agents, Immunological - therapeutic use; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - immunology; CD8-Positive T-Lymphocytes - immunology; Cetuximab - therapeutic use; CTLA-4 Antigen; Granzymes - immunology; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - immunology; Hepatitis A Virus Cellular Receptor 2 - immunology; Humans; Lymphocytes, Tumor-Infiltrating - immunology; Perforin - immunology; Programmed Cell Death 1 Receptor - immunology; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome
• ISSN: 2326-6074
• DOI: 10.1158/2326-6066.CIR-16-0333

Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8 tumor-infiltrating lymphocytes (TIL) and compared them with those of peripheral blood T lymphocytes (PBL) in patients with head and neck cancer (HNSCC) during cetuximab therapy. The frequency of PD-1 and TIM-3 expression was significantly increased in CD8 TILs compared with CD8 PBLs ( = 0.008 and = 0.02, respectively). This increased CD8 TIL population coexpressed granzyme B/perforin and PD-1/TIM-3, which suggests a regulatory role for these immune checkpoint receptors in cetuximab-promoting cytolytic activities of CD8 TILs. Indeed, the increased frequency of PD-1 and TIM-3 CD8 TILs was inversely correlated with clinical outcome of cetuximab therapy. These findings support the use of PD-1 and TIM-3 as biomarkers to reflect immune status of CD8 T cells in the tumor microenvironment during cetuximab therapy. Blockade of these immune checkpoint receptors might enhance cetuximab-based cancer immunotherapy to reverse CD8 TIL dysfunction, thus potentially improving clinical outcomes of HNSCC patients. .