Grabmeier-Pfistershammer, K.

bioRxiv2026

Tissue-resident memory T cells are diminished in the Kaposi sarcoma tumor microenvironment of people living with HIV

Kaposi sarcoma (KS) is a rare neoplasm and an AIDS-defining diagnosis in people living with HIV (PLWH). Although and chronic infection with Kaposi sarcoma-associated herpesvirus (KSHV) contributes to KS progression, the local immune mechanisms that are lost during tumor progression remain incompletely understood. Here, we systematically characterized global patterns in the KS tumor microenvironment (TME) in both PLWH and HIV-negative individuals. Spatial transcriptomics revealed distinct niches comprising of tumor cells, immune cells, and surrounding skin cells. Tumor regions expressed a characteristic endothelial-fibroblastic signature attributable to KS tumor cells (CD34, LYVE1, SCN9A), TME regions expressed marker genes for T cells, B cells and cancer-associated fibroblasts. Analysis of putative cell-cell interactions demonstrated that tumor cells preferentially interact with cells of the TME, including T cells, indicating an important role as hub of cellular communication in KS. Immunofluorescence imaging confirmed increased numbers of T cells, specifically tissue-resident memory T cells (TRM), in KS samples compared to healthy skin, accompanied by a pronounced upregulation of PD-1 expression that was predominantly localized to the TME. Notably, we identified HIV-associated alterations in the KS immune microenvironment: PLWH exhibited loss of CXCR3+ and IFN-gamma producing CD8+ TRM cells in the KS TME compared to HIV-negative patients, a finding consistent with impaired antitumor immunity. Together, our findings reveal HIV-associated disruption of functional anti-tumor immunity in the KS TME of PLWH. Increased PD-1 expression within T cells of the TME highlights potential therapeutic use of immune checkpoint inhibitors in KS.

immunology↗

bioRxiv2018

B cells sustain inflammation and improve survival in human melanoma

Tumor associated inflammation is one of important predictors of response to immune checkpoint blockade. Understanding molecular processes that regulate tumor inflammation is key to improve the efficacy of checkpoint blockade. Established mechanisms that underlie therapy response and resistance have centered on anti-tumor T cell responses.\n\nWe show that tumor-associated B cells are vital to T cell functions. They promote recruitment of CD8+ T cells through plasmablast-like cells with expression of pro- and anti-inflammatory factors. Plasmablast-like cells are associated with improved survival of patients with metastatic melanoma and their response to checkpoint blockade. Plasmablast-like B cells express chemokines for T cell-attraction. Depletion of tumor-associated B cells by anti-CD20 immunotherapy of metastatic melanoma patients causes a remarkable decrease in tumor CD8+ T cells. These findings indicate that tumor-associated B cells orchestrate and sustain tumor inflammation, recruit CD8+ T effector cells and are key to therapeutic response and patients overall survival.

cancer biology↗