HLA-I and Cancer

Immunological and clinical significance of HLA class I antigen processing machinery component defects in malignant cells.

Concha-Benavente F1, Srivastava R2, Ferrone S3, Ferris RL4.

1. Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.

2. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA.

3. Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.

4. Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA; Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. Electronic address: ferrisrl@upmc.edu.

Abstract

Experimental as well as clinical studies demonstrate that the immune system plays a major role in controlling generation and progression of tumors. The cancer immunoediting theory supports the notion that tumor cell immunogenicity is dynamically shaped by the immune system, as it eliminates immunogenic tumor cells in the early stage of the disease and then edits their antigenicity. The end result is the generation of a tumor cell population able to escape from immune recognition and elimination by tumor infiltrating lymphocytes. Two major mechanisms, which affect the target cells and the effector phase of the immune response, play a crucial role in the editing process. One is represented by the downregulation of tumor antigen (TA) processing and presentation because of abnormalities in the HLA class I antigen processing machinery (APM). The other one is represented by the anergy of effector immune infiltrates in the tumor microenvironment caused by aberrant inhibitory signals triggered by immune checkpoint receptor (ICR) ligands, such as programmed death ligand-1 (PD-L1). In this review, we will focus on tumor immune escape mechanisms caused by defects in HLA class I APM component expression and/or function in different types of cancer, with emphasis on head and neck cancer (HNC). We will also discuss the immunological implications and clinical relevance of these HLA class I APM abnormalities. Finally, we will describe strategies to counteract defective TA presentation with the expectation that they will enhance tumor recognition and elimination by tumor infiltrating effector T cells.

Oral Oncol. 2016 Jul;58:52-8. doi: 10.1016/j.oraloncology.2016.05.008. Epub 2016 Jun 2.

http://www.sciencedirect.com/science/article/pii/S1368837516300549

Md. PhD. Fernando Concha. Ex-miembro del GII