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International Journal of Clinical Oncology

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29-05-2022 | Human Immunodeficiency Virus | Original Article

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

Authors: Yasuo Matsubara, Yasunori Ota, Yukihisa Tanaka, Tamami Denda, Yasuki Hijikata, Narikazu Boku, Lay Ahyoung Lim, Yoshihiro Hirata, Giichiro Tsurita, Eisuke Adachi, Hiroshi Yotsuyanagi

Published in: International Journal of Clinical Oncology | Issue 8/2022

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.

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Title: 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
Authors: Yasuo Matsubara
Yasunori Ota
Yukihisa Tanaka
Tamami Denda
Yasuki Hijikata
Narikazu Boku
Lay Ahyoung Lim
Yoshihiro Hirata
Giichiro Tsurita
Eisuke Adachi
Hiroshi Yotsuyanagi
Publication date: 29-05-2022
Publisher: Springer Nature Singapore
Keywords: Human Immunodeficiency Virus
Colorectal Cancer
Colorectal Cancer
Published in: International Journal of Clinical Oncology / Issue 8/2022
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-022-02188-8

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