Work

Identifying the antigenic drivers of tertiary lymphoid structure formation in solid cancers 3205

Year: 2025

Type: article

Abstract: Description Tertiary Lymphoid Structures (TLSs) are ectopic lymphoid structures, formed in the presence of inflammation/tumors and are niches for antigen drainage. TLSs provide tumor-adjacent compartments to support cognate interactions of T follicular helper (Tfh) and B cells, which facilitate antigen-specific, anti-tumor responses. The presence of TLSs in solid tumors is associated with favorable prognosis. Despite the widely recognized importance of TLSs in cancer, the mechanisms behind their formation are poorly understood. We hypothesize that this process is driven by tumor antigens, but in absence of the knowledge of the antigens, it is difficult to understand their contribution to TLS formation. We posited that knowing the tumor antigens recognized by Tfh cells in tumor-associated TLSs will reveal the processes that lead to TLS formation and influence therapeutic outcome. In a murine melanoma model, we observed that intraperitoneal injections of B16-OVA tumor cells led to TLS formation. Upon confirming tumor-infiltrating Tfh cells by flow cytometry, we used scRNAseq to identify clonally expanded Tfh TCRs. We are currently using our lab’s antigen discovery platform to identify the tumor antigens recognized by the expanded Tfh TCRs and are aiming to perform spatial transcriptomics to identify TLS-specific Tfh antigens. These studies will uncover whether TLS formation is driven by tumor antigens and provide novel diagnostic and therapeutic targets to modulate TLS formation. Funding Sources Supported by: 5T32CA082084-23; UMPC Hillman Cancer Center Minnow Tank; NIH 1DP2AI176138-01 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1030

Authors: Mary Melissa Roland, Amy Zhou, Lyubov Kublo, Venkata Krishna Kanth Makani, Paul Zdinak, Alok V. Joglekar

Institution: University of Pittsburgh

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases