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Single-cell spatial multiomics reveals tumor microenvironment vulnerabilities in cancer resistance to immunotherapy

2024; Cell Press; Volume: 43; Issue: 7 Linguagem: Inglês

10.1016/j.celrep.2024.114392

2639-1856

Camelia Quek, Aditya Pratapa, Xinyu Bai, Ghamdan Al‐Eryani, Inês Pires da Silva, Aaron T. Mayer, Nenad Bartonicek, Kate Harvey, Nigel Maher, Jordan W. Conway, Rebecca J. Kasalo, Bassem Ben Cheikh, Oliver Braubach, Umaimainthan Palendira, Robyn P.M. Saw, Jonathan R. Stretch, Kerwin F. Shannon, Alexander M. Menzies, Richard A. Scolyer, Georgina V. Long, Alexander Swarbrick, James S. Wilmott,

CAR-T cell therapy research

Heterogeneous resistance to immunotherapy remains a major challenge in cancer treatment, often leading to disease progression and death. Using CITE-seq and matched 40-plex PhenoCycler tissue imaging, we performed longitudinal multimodal single-cell analysis of tumors from metastatic melanoma patients with innate resistance, acquired resistance, or response to immunotherapy. We established the multimodal integration toolkit to align transcriptomic features, cellular epitopes, and spatial information to provide deeper insights into the tumors. With longitudinal analysis, we identified an "immune-striving" tumor microenvironment marked by peri-tumor lymphoid aggregates and low infiltration of T cells in the tumor and the emergence of MITF