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| Main Authors: | , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Cell
2026
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41997129/ |
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Table of Contents:
- Mapping intratumor heterogeneity across layers for advancing immunotherapy. Marine, Jean-Christophe Bartok, Osnat Sagie, Shira Vitiello, Pietro Paolo Bardelli, Alberto Weller, Chen Chang, Tian-Gen Tonelli, Claudia Spranger, Stefani Ruppin, Eytan Samuels, Yardena Humans Immunotherapy Neoplasms Genetic Heterogeneity Animals T-Lymphocytes Tumor Microenvironment Antigen Presentation 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.