Antigen specific immune responses and mechanisms of impaired antigen presentation in HPV positive and negative head and neck cancer

Background: Antigen-specific immune response is a hallmark of cancer immunotherapy. Potential antigens in head and neck squamous cell carcinoma (HNSCC) include tumor-associated antigens (TAAs), mutation-associated neoantigens (MANAs) and viral proteins, including high-risk human papillomavirus (HPV) proteins. Studies combining multiple antigens for cellular therapy renewed interest in TAAs. While intratumoral expression of antigens is frequent, immunotherapy does not induce durable tumor regression in the majority of HNSCC patients. Impaired HLA class I antigen processing as a key factor of immune evasion in HNSCC has been recognized previously, but the precise mechanisms remain elusive.

Methods: RNA expression of TAAs and genes associated with antigen presentation were assessed by 3" RNA Sequencing of treatment naïve HPV-positive and HPV-negative HNSCC tumor samples and matched healthy mucosa. Endogenous T cell and humoral responses against viral proteins and TAAs were determined by FluoroSpot and protein-bound bead assays. Expression of components of the HLA class I antigen presentation pathway was analyzed in a large cohort of HPV-positive and HPV-negative HNSCC patients and correlated to intratumoral immune cell abundance.

Results/Conclusion: New results will be presented in the context of previously published literature regarding antigen-specific immune response and immune evasion in HNSCC.

H.A.S.: Funding for Research by Astra Zeneca and Tabby therapeutics; SAB for BMS.

J.P.K.: Honoraria for advisory boards from BMS, MSD, for invited talks from Astra Zeneca, BMS, MSD, Merck and financial support for research projects from MSD.

H.N.C.E.: Honoraria for advisory boards from MSD. All remaining authors declare no competing interests.