Journal Article

Immune escape of head and neck cancer mediated by the impaired MHC-I antigen presentation pathway

Fitzsimonds, Zackary R., Wang, Qiuhao, Luo, Xiaobo, Qiu, Yan, Lei, Yu Leo, Chen, Qianming

2024

Overview

Tumor immune evasion is a hallmark of Head and Neck Cancers. The advent of immune checkpoint inhibitors (ICIs) in the first-line setting has transformed the management of these tumors. Unfortunately, the response rate of Head and Neck Squamous Cell Carcinomas (HNSCC) to ICIs is below 15%, regardless of the human papillomavirus (HPV) status, which might be partially related with impaired antigen presentation machinery (APM). Mechanistically, HNSCC cells are usually defective in the expression of MHC-I associated APM, while this transcriptional pathway is critical for the activation of tumor-killing effector T-cells. To specifically illuminate the phenomenon and seek for therapeutic strategies, this review summarizes the most recently identified role of genetic and functional dysregulation of the MHC-I pathway, specifically through changes at the genetic, epigenetic, post-transcriptional, and post-translational levels, which substantially contributes to HNSCC immune escape and ICI resistance. Several treatment modalities can be potentially exploited to restore APM signaling in tumors, which improves anti-tumor immunity through the activation of interferons, vaccines or rimantadine against HPV and the inhibition of EGFR, SHP-2, PI3K and MEK. Additionally, the combinatorial use of radiotherapy or cytotoxic agents with ICIs can synergize to potentiate APM signaling. Future directions would include further dissection of MHC-I related APM signaling in HNSCC and whether reversing this inhibition in combination with ICIs would elicit a more robust immune response leading to improved response rates in HNSCC. Therapeutic approaches to restore the MHC-I antigen presentation machinery in Head and Neck Cancer. (Red color texts represent the according strategies and the outcomes).

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 1-Phosphatidylinositol 3-kinase / 631/250/21 / 631/67/1536/1665 / 692/53/2422 / Antigen Presentation / Apoptosis / Cell Biology / Cytotoxic agents / Cytotoxicity / Effector cells / Epigenetics / Head & neck cancer / Head and neck carcinoma / Head and Neck Neoplasms - genetics / Human Genetics / Human papillomavirus / Humans / Immune checkpoint inhibitors / Immune evasion / Immune response / Interferons / Internal Medicine / Lymphocytes T / Major histocompatibility complex / Medicine / Medicine & Public Health / Oncology / Papillomavirus Infections / Post-transcription / Post-translation / Radiation therapy / Review Article / SHP-2 protein / Signal transduction / Squamous cell carcinoma / Squamous Cell Carcinoma of Head and Neck - genetics / Synergism / Tumors