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

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.