Literature DB >> 29362132

HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

Sara I Pai1, J Jack Lee2, Thomas E Carey3, William H Westra4, Soldano Ferrone5, Charles Moore6, Marina B Mosunjac7, Dong M Shin8, Robert L Ferris9.   

Abstract

Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy.
Copyright © 2017 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Antigen processing machinery; Head and neck cancer; Human Papillomavirus; Human immunodeficiency virus; Immune checkpoint blockade; PD-1; PD-L1

Mesh:

Substances:

Year:  2017        PMID: 29362132      PMCID: PMC5786382          DOI: 10.1016/j.oraloncology.2017.12.014

Source DB:  PubMed          Journal:  Oral Oncol        ISSN: 1368-8375            Impact factor:   5.337


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