Biology subjects

Bortolatto, J.

Publications and source records attributed to Bortolatto, J..

2 recordsLinked to original sources

bioRxiv2022

Proximity-dependent labeling identifies dendritic cells that prime the antitumor CD4+ T cell response

Dendritic cells (DCs) are uniquely capable of transporting tumoral antigens to tumor-draining lymph nodes (tdLNs), and also interact with effector T cells within the tumor microenvironment (TME) itself, mediating both natural antitumor immunity and the response to checkpoint blockade immunotherapy. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)-based single-cell transcriptomics, we identify individual DCs capable of presenting antigen to CD4+ T cells in the tdLN as well as inside the tumor microenvironment (TME). Our findings reveal that DCs with similar hyperactivated transcriptional phenotypes interact with helper T cells both within tumors and in the tdLN, and that checkpoint blockade drugs enhance these interactions. These findings show that a relatively small fraction of DCs is responsible for most of the antigen presentation within the tdLN and TME to both CD4+ and CD8+ tumor-specific T cells and that classical checkpoint blockade enhances CD40-driven DC activation at both sites.

immunology↗

bioRxiv2021

Vγ usage distinguishes pro- and anti-tumor intestinal γδ T cell subsets

{gamma}{delta} T cells physiologically scan the intestinal epithelium, representing a substantial fraction of infiltrating lymphocytes in colorectal cancer (CRC), albeit their role in CRC remains unclear. Using murine CRC models, we found that most {gamma}{delta} T cells in pre- or non-tumor colon express V{gamma}1+ or V{gamma}7+ and exhibit a cytotoxic profile. Targeting these {gamma}{delta} T cell subsets, as well as conditionally interfering with {gamma}{delta} T cell function at early stages of tumorigenesis led to heightened tumor development, suggesting anti-CRC functions for V{gamma}1+ and V{gamma}7+ subsets. In contrast, ROR{gamma}t+ {gamma}{delta} T cell subsets, including V{gamma}4+ and microbiotadependent V{gamma}6+, accumulated during CRC progression. Conditional deletion of ROR{gamma}t or V{gamma} chains revealed redundant roles for IL-17-producing V{gamma}4+ and V{gamma}6+ {gamma}{delta} T cells in promoting tumor growth. Our results uncover pro- and anti-tumor roles for {gamma}{delta} T cell subsets.

immunology↗