本文采用的英格恩产品: 增强型ECL发光液
Mapping intratumor heterogeneity across layers for advancing immunotherapy
Affiliations
- 1 Laboratory for Molecular Cancer Biology, Center for Cancer Biology, VIB, Leuven, Belgium; Laboratory for Molecular Cancer Biology, Department of Oncology, KULeuven, Leuven, Belgium.
- 2 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
- 3 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Jusidman Cancer Center, Sheba Medical Center, 52621 Ramat Gan, Israel.
- 4 Department of Oncology, Molecular Biotechnology Center, University of Torino, 10126 Turin, Italy; IFOM ETS, The AIRC Institute of Molecular Oncology, 20139 Milan, Italy.
- 5 Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
- 6 Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA; Department of Biology, MIT, Cambridge, MA, USA; Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA.
- 7 Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Translational Research Institute, The Jim and Eleanor Randall Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
- 8 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: yardena.samuels@weizmann.ac.il.
- PMID: 41997129
- PMCID: PMC13283290
- DOI: 10.1016/j.cell.2026.03.025
Abstract
Intratumor heterogeneity (ITH) encompasses genetic, epigenetic, transcriptional, proteomic, and immunopeptidomic diversity. Beyond genetic heterogeneity, it is increasingly clear that non-mutational heterogeneity and plasticity generate dynamic cancer cell states with distinct immune visibility. These layers of complexity converge on the immunopeptidome, the repertoire of peptides displayed by major histocompatibility complex molecules through which tumor cells are surveyed by T cells. Variation in antigen processing, presentation, and peptide abundance across cancer clones and cell states yields spatially and temporally distinct immunological niches that shape immune recognition and therapeutic response. Here, we summarize how multidimensional ITH manifests across cancer types and constrains immunotherapy efficacy. We propose that integrating measurements across layers is a promising direction for improving biomarker identification and informing more precise immune-based treatment strategies.
