HIV status alters immune cell infiltration and activation profile in women with breast cancer

• Published in: Nature communications Vol. 16; no. 1; pp. 4699 - 14
• Main Authors: Bauer, Marcus, Santos, Pablo, Wilfer, Andreas, van den Berg, Eunice, Zietsman, Annelle, Vetter, Martina, Kaufhold, Sandy, Wickenhauser, Claudia, dos-Santos-Silva, Isabel, Chen, Wenlong Carl, Cubasch, Herbert, Murugan, Nivashini, McCormack, Valerie, Joffe, Maureen, Seliger, Barbara, Kantelhardt, Eva
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.05.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/51; 13/95; 14/34; 14/63; 38/39; 38/90; 631/250/580; 631/326/596/2557; 692/308/174; 692/4028/67/1347; Adult; Aged; Breast cancer; Breast Neoplasms - complications; Breast Neoplasms - immunology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - virology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; ErbB-2 protein; Female; HIV; HIV Infections - complications; HIV Infections - immunology; HIV Infections - virology; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Immune system; Immunosurveillance; Infiltration; Interferon-gamma - metabolism; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Metastases; Middle Aged; multidisciplinary; Namibia; Science; Science (multidisciplinary); South Africa; Survival; Tumor microenvironment; Tumor Microenvironment - immunology; Tumors; γ-Interferon; South Africa; Namibia
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-025-59408-8

The breast cancer (BC)-related mortality is higher and the immunity is altered in women living with HIV (WLWH) compared to HIV-negative women. Therefore, tumor samples of 296 black BC patients from South Africa and Namibia with known age, HIV status, tumor stage, hormone receptor and HER2 status and overall survival (OS) are analyzed for components of the tumor microenvironment (TME). WLWH ( n  = 117), either with suppressed viral activity (HR = 1.25) or with immune suppression (HR = 2.04), have a shorter OS. HIV status is associated with increased numbers of CD8 + T cells in the TME compared to HIV-negative patients; no correlation is found with CD4 + T cell numbers in the blood. Moreover, an increased expression of CD276/B7-H3 and a more pronounced IFN-γ signaling in the tumors are found in WLWH, independent of age, stage, and BC subtypes. In conclusion, altered T cell composition and CD276 expression in WLWH may contribute to inferior survival and can be used for targeted treatment. Cancer is subject to immune surveillance, and HIV infection dampens immune capacity, but HIV-induced immune alterations in patients with breast cancer is still unclear. Here the authors profile women living with HIV to find increased CD8 T cell tumor infiltration, enhanced checkpoint molecular expression, and reduced overall survival when compared with controls.