# (PQ1) Lipid Metabolism, Inflammation, and T cell Dysfunction in HIV-associated Cancer

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $630,537

## Abstract

Patients with HIV infection have higher incidence of many cancers and often with a poorer prognosis, despite
effective antiretroviral therapy and cancer-targeted therapy. Given that T cell exhaustion has been strongly
implicated in cancer incidence and outcome, understanding the connection between chronic, persistent
inflammation and T cell dysfunction is critical among patients with HIV who develop cancer. Our preliminary
murine data shows that exposure to fatty acids promotes properties of T cell exhaustion (such as increased
PD-1 expression and suppression of effector functions). We also find that free fatty acids (FFAs) levels are
significantly higher in murine models of chronic viral infection and melanoma compared to healthy controls, two
settings in which functionally exhausted PD-1hi T cells are present. Based on these data and preliminary data
in HIV infected individuals, we propose that the presence and persistence of lipid dysregulation results in an
aggressively pro-inflammatory environment that directly contributes T cell dysfunction and increased PD-1
expression. The high rate of metabolic syndrome among HIV-infected individuals, due to viral infection and
antiretroviral therapy itself, further contributes to inflammation and T cell dysfunction. We will thus explore
whether there is a direct correlation between lipid dysregulation and T cell exhaustion in HIV-infected patients
and whether presence of exhausted T cells results in increased cancer incidence in this population. By
utilizing a well-established longitudinal cohort, we are in a unique position to address the role of immune
dysfunction and lipid metabolism upon increased cancer incidence among HIV-infected individuals. In
addition, we will use both HIV-infected subject samples and a murine model of chronic viral infection to
determine the impact of elevated circulating FFA and fatty acid uptake on T cell exhaustion. Our aims will (1)
establish a link between lipid dysregulation and T cell exhaustion in HIV-infected individuals, among HIV-
infected individuals who develop cancer, and in tumor tissue from HIV-infected individuals; (2) define the
mechanism by which free fatty acid (FFA) uptake, via transporters such as CD36, impacts T cell dysfunction in
a murine model of chronic infection, a murine model of cancer, and in HIV-infected individuals; Understanding
the inflammatory link between metabolic syndromes and immunosuppressive tumor environment is important
to discover new targets to prevent and/or treat cancer, which may include interventions targeting fatty acid
signaling.

## Key facts

- **NIH application ID:** 10174850
- **Project number:** 5R01CA206483-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** BRINDA EMU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $630,537
- **Award type:** 5
- **Project period:** 2017-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174850

## Citation

> US National Institutes of Health, RePORTER application 10174850, (PQ1) Lipid Metabolism, Inflammation, and T cell Dysfunction in HIV-associated Cancer (5R01CA206483-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10174850. Licensed CC0.

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