Wednesday, December 17, 2025 12/17/2025

Tumor-associated pDC (TApDC) in liver cancer with HIV infection

Award Number: R01CA298839
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/05/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2029

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Tumor-associated pDC (TApDC) in liver cancer with HIV infection - The long-term goals are to study functions of tumor-associated plasmacytoid dendritic cells (TApDC) in tumor immune microenvironment (TIME) of liver cancer or hepatocellular carcinoma (HCC) during HIV infection and immunotherapy, and to develop novel therapeutics to treat HCC in HIV-infected patients, which has a disproportionate impact on African American and African/Asian immigrant communities. Current combination antiretroviral therapy (cART) has increased life span for people with HIV (PWH). However, PWH patients experience accelerated immunological aging (inflammaging) which is characterized by up-regulation of inflammatory cytokines, immune dysfunction, and end-organ diseases such as liver cancer/HCC. One major recent advancement in liver cancer immunotherapy is to use combined immune checkpoint inhibitors (ICI) CTLA- 4 and PD-1 (PD-L1) blocking antibodies to elevate anti-tumor immunity. Current anti-CTLA-4 antibodies used clinically exhibit suboptimal cancer immunotherapeutic effect (ITE), but they also lead to serious immunotherapy- related adverse events (irAE). Our preliminary results show that i) pDC depletion in hu-mice with HIV infection and effective cART rescued anti-HIV CD8+ T cells to control HIV-1 persistence in HIV-infected humanized mice. ii) pDC depletion resolved inflammation-related tissue injury, reversed immune exhaustion and restored activity in CD8+ T cells, including TCF1+ PD1+ TIM3- stem-like CD8 T cells in number and functions. iii) In NSG-based humanized immune/tumor model (HCC-HIT mice), human tumors grew faster than in NSG mice, associated with abundant tumor-associated pDC (TApDC), elevated TA-Treg and exhausted (TCF1-PD1-TIM3+) T cells, but reduced stem-like CD8 T cells. iv) Depletion of TApDC in human HCC-HIT mice reduced HCC growth and rescued stem-like CD8 T cells in number and functions, associated with depletion of TA-Treg. We hypothesis that TApDC in HCC TIME are further elevated by HIV/cART and contributes to both immune suppression in promoting liver cancer and to irAE during ICI immunotherapy of HCC. Depletion of TApDC during ICI therapy may i) lead to depletion of TA-Treg and ii) rescue stem-like CD8 T cells that respond to PD-1 ICI. We propose the following specific aims to test the idea. Specific Aim 1 will study how TApDC reprogram HCC TIME in HCC- HIT mice +/- HIV. We will also define how HIV infection affects TApDC/TIME in HCC-HIT mice and characterize human TApDC after HCC induction +/- HIV infection. TApDC depletion affects human HCC growth in HCC-HIT mice +/- HIV infection and how Specific Aim 2 will define how TApDC modulates anti-tumor specific T cells and enhance CITE of PD1 ICIs in mice. We hypothesize that depletion of TApDC in combination with PD1 mAb will enhance its CITE by reducing Treg and increasing stem-like CD8 T cells that respond to anti-PD1 mAb. Aim 3 will investigate how TApDC interact with ICIs to modulate CITE and irAE in HCC-HIT mice+HIV. We postulate that depletion of TApDC in HCC will not only enhance PD1 ICI-associated CITE but also mitigate its irAE in HCC- HIT mice. Key findings will be confirmed in future clinical studies in HCC patients with and without HIV infection.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $570,655 )
2026	2026	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Biology Research	000	2	12/11/2025	NON-COMPETING CONTINUATION	$570,655
														Subtotal = $570,655

Issue Date FY: 2025 ( Subtotal = $634,061 )
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Biology Research	000	1	12/5/2024	NEW	$634,061
														Subtotal = $634,061

Grand Total All Awards = $1,204,716

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Tumor-associated pDC (TApDC) in liver cancer with HIV infection

Award Number: R01CA298839

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/05/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2029

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