Abstract 120: A closer Look at colorectal cancer risk: Insights from the complex relationship of HIV, helminths, and immune responses

Abstract The advent of antiretroviral therapy has markedly increased the survival rates of individuals with human immunodeficiency virus (HIV). However, this demographic, particularly in low-middle-income countries (LMICs) where HIV-helminth co-infections are prevalent, remains susceptible to infections. The intricate interplay between helminth infections and HIV susceptibility, often inducing immunological phenotypes that heighten vulnerability, remains poorly understood. Studies have shown the association between HIV-helminth co-infections and elevated susceptibility to colorectal cancer (CRC), introducing an additional layer of health concerns for this already vulnerable population. This retrospective observational study delves into the profound effects of HIV-helminth co-infections on immune responses, with a specific focus on type 2 T helper (Th2) cell immunomodulation and susceptibility to CRC. Utilizing samples from a master project (n=414), 80 systematically randomized individuals were categorized into uninfected control, HIV-infected only, helminth-infected only, and HIV-helminth co-infected groups. Parasite detection employed the Kato-Katz technique, and serum testing was conducted for helminth-specific antibodies. Serological HIV testing, viral load categorization, white blood cell counts, and differential analyses were performed. Human ProcartaPlex Panel 1 was used for cytokine profiling of immune stimulatory and inhibitory soluble proteins. A significant reduction in B and T lymphocyte attenuator (BTLA) (p=0.049) in helminth infections compared to the control. The association of BTLA with its ligand, herpesvirus entry mediator (HVEM), establishes a direct link between the CD28 and tumor necrosis factor receptor (TNFR) families, triggering wide-ranging and robust immune responses. Subsequently, a notable reduction in CD28 was observed in HIV-infected subjects (p=0.003), followed by helminth-infected and HIV-helminth co-infected individuals (p=0.03) compared to the control. Furthermore, programmed death ligand-2 (PD-L2) expression, a major contributor to alternatively activated macrophage polarization during helminth infections, was significantly increased in the HIV-helminth co-infected group (p = 0.05), favoring a shift towards Th2 immune responses. These observed alterations underscore the complexity of the immunological interplay in co-infected individuals, emphasizing an additional risk factor for colorectal cancer development. This necessitates a comprehensive understanding, providing valuable insights for the development of therapeutic strategies in LMICs and similar settings, addressing the heightened risk of CRC within this population. Citation Format: Botle P. Damane, Thanyani V. Mulaudzi, Sayed S. Kader, Ropo E. Ogunsakin, Pragalathan Naidoo, Zodwa Dlamini, Zilungile L. Mkhize-Kwitshana. A closer Look at colorectal cancer risk: Insights from the complex relationship of HIV, helminths, and immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 120.