Altered mucosal immunity in HIV-positive colon adenoma: decreased CD4+ T cell infiltration is correlated with nadir but not current CD4+ T cell blood counts

Abstract

Background: People living with HIV (PLWH) face greater risks of developing non-AIDS-defining cancers (NADCs) than the general population; however, the underlying mechanisms remain elusive. The tumor microenvironment plays a significant role in the carcinogenesis of colorectal cancer (CRC), an NADC. We studied this carcinogenesis in PLWH by determining inflammatory phenotypes and assessing PD-1/PD-L1 expression in premalignant CRC stages of colon adenomas in HIV-positive and HIV-negative patients.

Methods: We obtained polyp specimens from 22 HIV-positive and 61 HIV-negative participants treated with colonoscopy and polyp excision. We analyzed adenomas from 33 HIV-positive and 99 HIV-negative patients by immunohistochemistry using anti-CD4, anti-CD8, anti-FoxP3, and anti-CD163 antibodies. Additionally, we analyzed the expression levels of immune checkpoint proteins. We also evaluated the correlation between cell infiltration and blood cell counts.

Results: HIV-positive participants had fewer infiltrating CD4⁺ T cells than HIV-negative participants (p = 0.0016). However, no statistical differences were observed in infiltrating CD8⁺ and FoxP3⁺ T cells and CD163⁺ macrophages. Moreover, epithelial cells did not express PD-1 or PD-L1. Notably, CD4⁺ T cell infiltration correlated with nadir blood CD4⁺ T cell counts (p < 0.05) but not with current blood CD4⁺ T cell counts.

Conclusion: Immune surveillance dysfunction owing to decreased CD4⁺ T cell infiltration in colon adenomas might be involved in colon carcinogenesis in HIV-positive individuals. Collectively, since the nadir blood CD4⁺ T cell count is strongly correlated with CD4⁺ T cell infiltration, it could facilitate efficient follow-up and enable treatment strategies for HIV-positive patients with colon adenomas.

Keywords: CD4+ T cells; Colon adenomas; HIV; Tumor microenvironment.