Project description:DeepNeo predicts immunogenic neoantigens for both MHC I and II responsive to immune checkpoint blockade therapy. Furthermore, spontaneous immunity was observed in pancancer manner for MHC II.
Project description:To comprehensively characterize the changes within the TME during TREM1 deficiency and anti-PD-1 immune checkpoint blockade therapy, we performed scRNA-seq analysis of the CD45+ TICs in melanoma-bearing C57BL/6 mice receiving the various treatments. We analyzed approximately 8,249 CD45+ cells from the treatment groups with t-SNE analysis, identifying 10 distinct clusters of tumor-infiltrating immune cells
Project description:Inhibition of integrin alpha-V/beta-6 sparks T-cell anti-tumor response and enhances immune checkpoint blockade therapy in colorectal cancer
Project description:The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for anti-tumor responses and effective immune checkpoint blockade (ICB) therapy. Here we show that human CD1c+CD5+ dendritic cells are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T-cell priming and improved survival after immune checkpoint blockade therapy. CD5+ DC numbers increased during ICB treatment, and low IL-6 levels promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5hi T helper and CD8+ T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Thus, CD5+ dendritic cells are an essential component of optimal immune checkpoint blockade therapy.
Project description:Interleukin-34 (IL-34) is an alternative ligand to colony-stimulating factor-1 (CSF-1) for the CSF-1 receptor that acts as a key regulator of monocyte/macrophage lineage. In this study, we show that cancer cells-derived IL-34 mediates resistance to immune checkpoint blockade regardless of CSF-1 existence. In a therapeutic study of a programmed death-1 and cytotoxic T-lymphocyte-associated antigen-4 blocking monoclonal antibody, the expression of IL-34 in tumors was accompanied with limited benefits compared to IL-34 non-expressing tumors in various murine cancer models. Consistent with its immunosuppressive characteristics, the expression of IL-34 in tumors correlates with decreased frequencies of cellular (such as CD8+ and CD4+ T cells) and molecular (including various cytokines and chemokines) effectors at the tumor microenvironment. In addition, IL-34 blockade expands the M1-macrophage population. Then, a neutralizing antibody against IL-34 helped to reverse these effects and improved the therapeutic effects of the immune checkpoint blockade in combinatorial therapeutic models, including a patient-derived xenograft model of primary lung adenocarcinoma. Collectively, we revealed that tumor-derived IL-34 inhibits the efficacy of immune checkpoint blockade and proposed the utility of IL-34 blockade as a new strategy for cancer therapy.
Project description:Checkpoint blockade immunotherapy is a promising strategy in cancer treatment, depending on a favorable preexisting tumor immune microenvironment. However, prostate cancer is usually considered as an immune “cold” tumor with the poor immunogenic response and low density of tumor-infiltrating immune cells. This research uses samples from prostate cancer patients showing that docetaxel-based chemohormonal therapy reprograms the immune microenvironment and increases tumor-infiltrating T cells. Mechanistically, docetaxel treatment activates the cGAS/STING pathway and induces the type I interferon signaling, which may boost T cell-mediated immune response. In a murine prostate cancer model, chemohormonal therapy sensitizes tumor-bearing mice to PD1-blockade therapy. These findings demonstrate that docetaxel-based chemohormonal therapy activates prostate cancer immunogenicity and acts cooperatively with anti-PD-1 checkpoint blockade, providing a combination immunotherapy strategy that would lead to better therapeutic benefit for prostate cancer.
