Antigen Presentation in the Tumor Ecosystem

Diverse subsets of antigen-presenting cells (APCs) reside within solid tumors and have the potential to capture and present cancer antigens locally. The cellular and molecular interactions, as well as the challenges and outcomes of intratumoral cancer antigen presentation are poorly understood. Our laboratory has recently pioneered studies demonstrating that fibroblasts present cancer antigens to CD4 T cells within lung tumors. We proposed a model wherein intratumoral APCs sustain CD4 T cells independently of lymph nodes, known as the “Second Touch Hypothesis.” Currently, we are exploring the landscape of lung cancer APCs and seeking to understand how the tumor microenvironment affects them. During the first part of my talk, I will showcase space-aware transcriptomic maps of mesenchymal APCs in human lung tumors. I will pinpoint two subsets of antigen-presenting mesenchymal cells with different organization patterns in tumor ecosystems: an alveolar epithelial–derived and a myeloid cell–derived. In the second part, I will reveal a double-edged sword function for type I interferons. Specifically, I will explain how interferon-inducible GBP-2 induces pyroptotic death in intratumoral dendritic cells. By elucidating the complexities of cancer antigen-presenting cells, my laboratory aims to pave new pathways to more effective cancer immunotherapies.