Oren Barboy, Akhiad Bercovich, Hanjie Li, Yaniv Eyal-Lubling, Adam Yalin, Yuval Shapir Itai, Kathleen Abadie, Mor Zada, Eyal David, Shir Shlomi-Loubaton, Yonatan Katzenelenbogen, Diego Adhemar Jaitin, Chamutal Gur, Ido Yofe, Tali Feferman, Merav Cohen, Rony Dahan, Evan W Newell, Aviezer Lifshitz, Amos Tanay, Ido Amit
Successful immunotherapy relies on triggering complex responses involving T cell dynamics in tumors and the periphery. Characterizing these responses remains challenging using static human single-cell atlases or mouse models. To address this, we developed a framework for in vivo tracking of tumor-specific CD8+ T cells over time and at single-cell resolution. Our tools facilitate the modeling of gene program dynamics in the tumor microenvironment (TME) and the tumor-draining lymph node (tdLN). Using this approach, we characterize two modes of anti-programmed cell death protein 1 (PD-1) activity, decoupling induced differentiation of tumor-specific activated precursor cells from conventional type 1 dendritic cell (cDC1)-dependent proliferation and recruitment to the TME...
March 1, 2024: Nature Cancer