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

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.

GNAI2 Is a Risk Factor for Gastric Cancer: Study of Tumor Microenvironment (TME) and Establishment of Immune Risk Score (IRS)

“…Growing evidence suggests that cytokine activation [30], increased immune cell infiltration [31], accumulation of Oxidative Medicine and Cellular Longevity regulatory T cells [7], activation of the PD-1/PD-L1 pathway [32], and upregulation of inhibitory molecules [33] can lead to an immune dysfunction of the TME and produce an inflammatory TME [34]. Based on the above studies, it was confirmed that GNAI2 promotes the interaction between many inflammatory factors to influence the TME in GC.…”

Impact of human immunodeficiency virus status on laryngeal cancer survival and locoregional control

“…5,13 There is conflicting evidence regarding whether HIV+ HNSCC represents an etiologically distinct disease process from HNSCC in the general population. 3,15 In favor of such a distinction, HIV+ HNSCC has been found to have a unique mutation pattern in the TP53 tumor suppressor gene. 16 This specific mutation in HIV+ HNSCC suggests that HIV infection may play a direct role in pathogenesis of the cancer.…”

“…8 There is also evidence to suggest that chronic exposure to HIV viral antigens results in PD1-regulated T-cell exhaustion, contributing to disease progression. 2,3,15,17 However, there is also some evidence against a causal role of HIV in the development of HNSCC. There has been a progressive increase in the incidence of non-HIV related cancers among PLWH despite cART, and compared to PLWH on cART, untreated individuals have not been found to have an increased risk of HNSCC.…”

Systemic treatment and radiotherapy for patients with non-small cell lung cancer (NSCLC) and HIV infection – A systematic review

“…The rationale behind this exclusion is that the extent and type of response mounted by the immune system to lung cancer in these patients is mostly unknown and, therefore, there is a concern that response to immunotherapy may be suboptimal compared to HIV non-infected pa-tients. Yet, pre-clinical studies in PLWH patients with NSCLC [54], anal cancer [55] and head&neck cancer [56] revealed no dramatic differ-ences in tumors' immune infiltrate between HIV-infected vs HIV-uninfected patients. Curiously, in the case-control study with NSCLC patients [54], immune-cell infiltration was more pronounced in tumors from PLWH: there was a higher amount of CD8 + T cells, B cells (CD20 + ) and macrophages (CD163 + ).…”