A minimal gene set characterizes TIL specific for diverse tumor antigens across different cancer types
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| Vydáno v: | Nature Communications vol. 16, no. 1 (2025), p. 1070 |
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| Vydáno: |
Nature Publishing Group
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| On-line přístup: | Citation/Abstract Full Text - PDF |
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MARC
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| 022 | |a 2041-1723 | ||
| 024 | 7 | |a 10.1038/s41467-024-55059-3 |2 doi | |
| 035 | |a 3163047421 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 084 | |a 145839 |2 nlm | ||
| 245 | 1 | |a A minimal gene set characterizes TIL specific for diverse tumor antigens across different cancer types | |
| 260 | |b Nature Publishing Group |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Identifying tumor-specific T cell clones that mediate immunotherapy responses remains challenging. Mutation-associated neoantigen (MANA) -specific CD8+ tumor-infiltrating lymphocytes (TIL) have been shown to express high levels of CXCL13 and CD39 (ENTPD1), and low IL-7 receptor (IL7R) levels in many cancer types, but their collective relevance to T cell functionality has not been established. Here we present an integrative tool to identify MANA-specific TIL using weighted expression levels of these three genes in lung cancer and melanoma single-cell RNAseq datasets. Our three-gene “MANAscore” algorithm outperforms other RNAseq-based algorithms in identifying validated neoantigen-specific CD8+ clones, and accurately identifies TILs that recognize other classes of tumor antigens, including cancer testis antigens, endogenous retroviruses and viral oncogenes. Most of these TIL are characterized by a tissue resident memory gene expression program. Putative tumor-reactive cells (pTRC) identified via MANAscore in anti-PD-1-treated lung tumors had higher expression of checkpoint and cytotoxicity-related genes relative to putative non-tumor-reactive cells. pTRC in pathologically responding tumors showed distinguished gene expression patterns and trajectories. Collectively, we show that MANAscore is a robust tool that can greatly enrich candidate tumor-specific T cells and be used to understand the functional programming of tumor-reactive TIL.Although individual genes that distinguish tumor-reactive CD8+ T cells from bystander T cells in tumors have been described, a functionally meaningful integrative signature has not been established. Here authors show that mutation-associated neoantigen-specific CD8+ tumor-infiltrating lymphocytes can be recognized by MANAscore, an algorithm that uses weighted expression levels of CXCL13, ENTPD1 and IL7R in single-cell RNAseq datasets of lung cancer and melanoma patients as input. | |
| 653 | |a Cytotoxicity | ||
| 653 | |a Endogenous retroviruses | ||
| 653 | |a Tumors | ||
| 653 | |a Algorithms | ||
| 653 | |a Immunotherapy | ||
| 653 | |a Genes | ||
| 653 | |a Lymphocytes T | ||
| 653 | |a Lung cancer | ||
| 653 | |a Neoantigens | ||
| 653 | |a Mutation | ||
| 653 | |a CXCL13 protein | ||
| 653 | |a Antigen (tumor-associated) | ||
| 653 | |a Antigens | ||
| 653 | |a Melanoma | ||
| 653 | |a Immunological memory | ||
| 653 | |a Lymphocytes | ||
| 653 | |a Datasets | ||
| 653 | |a Interleukin 7 receptors | ||
| 653 | |a Gene expression | ||
| 653 | |a Functional programming | ||
| 653 | |a Cloning | ||
| 653 | |a Tumor-infiltrating lymphocytes | ||
| 653 | |a PD-1 protein | ||
| 653 | |a CD8 antigen | ||
| 653 | |a Environmental | ||
| 773 | 0 | |t Nature Communications |g vol. 16, no. 1 (2025), p. 1070 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3163047421/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3163047421/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |