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Functional Interrogation of Germinal Center Independent Memory B Cells in Head and Neck Cancer

Award Number: F31CA298182
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/01/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Functional Interrogation of Germinal Center Independent Memory B Cells in Head and Neck Cancer - PROJECT SUMMARY/ABSTRACT Current immunotherapies aim to reinvigorate dysfunctional or “exhausted” T cells, and while immunotherapies like anti-PD1 have improved the prognosis of patients with head and neck squamous cell carcinoma (HNSCC), most patients fail to produce a durable response. B cells represent a new possible target as they correlate with increased patient survival and immunotherapeutic response. Further, B cells directly potentiate the antitumor immune response locally and peripherally by producing tumor-specific antibodies that assist in cytotoxic effector functions that mediate tumor cell clearing, and through the generation of antigen-specific memory B cells (MBCs). Together, these data highlight MBCs as a promising target for new immunotherapeutic options to complement T-cell centric therapies; however, there is a clear knowledge gap in mechanistically understanding MBC function in the tumor microenvironment. MBCs are a heterogenous population with functionally distinct subsets and may be generated either from germinal center (GC)-dependent reactions or GC-independent reactions, that often predominate in chronic infections. In HNSCC, GC-independent MBCs accumulate in patient peripheral blood and tumors and correlate with advanced stage disease. Chronic antigen stimulation promotes the development of GC-independent MBCs, which are dysfunctional compared to GC-dependent MBCs i.e. hyporesponsive to BCR stimulation, impaired differentiation to antibody secreting cells, and poor effector (IgG) antibody production. Moreover, we find that GC-independent MBCs express high levels of inhibitory receptors, such as PD-1 and FcRL5, further suggesting this population is functionally impaired in the tumor microenvironment. Importantly, despite low antibody production, GC-independent MBCs predominantly produce IgG antibodies, posing this MBC subset as an antigen specific population that can contribute to antitumor immunity through the production of tumor reactive antibodies. Our overarching hypothesis is that GC- independent MBCs are a tumor-specific B cell subset in the tumor microenvironment that can be therapeutically bolstered to secrete tumor-reactive antibodies. This proposal will (1) identify tumor reactive GC-independent MBCs in the tumor microenvironment and assess their potential to contribute to tumor cell clearance; and (2) interrogate therapeutic modulation of these populations, evaluating response to standard of care immunotherapies i.e. anti-PD1 treatment and combinatorial FcRL5 blockade. Successful completion of this proposal will provide preclinical rationale for B-cell centric therapies in tandem with current immunotherapy strategies for the treatment of solid tumors.


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 = $50,114 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Research Manpower	000	2	7/29/2026	NON-COMPETING CONTINUATION	$50,114
														Subtotal = $50,114

Issue Date FY: 2025 ( Subtotal = $49,538 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Research Manpower	000	1	7/16/2025	NEW	$49,538
														Subtotal = $49,538

Grand Total All Awards = $99,652

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Functional Interrogation of Germinal Center Independent Memory B Cells in Head and Neck Cancer

Award Number: F31CA298182

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/01/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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