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The 12-CK Score: Global Measurement of Tertiary Lymphoid Structures

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FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.694079

关键词

tertiary lymphoid structures; 12-CK score; immune checkpoint blockade; prognostic biomarker; predictive biomarker

资金

  1. Clinical Science Division at Moffitt Cancer Center
  2. Campbell Family Foundation
  3. Biostatistics and Bioinformatics Shared Resource at H. Lee Moffitt Cancer Center and Research Institute, a NCI designated Comprehensive Cancer Center [P30-CA076292]
  4. NCI-NIH [1R01 CA148995, 1R01 CA184845, P30 CA076292, P50 CA168536]
  5. Cindy and Jon Gruden Fund
  6. Chris Sullivan Fund
  7. V Foundation
  8. Dr. Miriam and Sheldon G. Adelson Medical Research

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The study highlights the importance of tertiary lymphoid structures in the tumor microenvironment, their association with favorable outcomes in tumors, and predictability of response to immune checkpoint blockade. The 12-CK score has been validated as a prognostic marker for survival in various tumor types, including melanoma, breast cancer, and bladder cancer.
There is emerging evidence that the adaptive anti-tumor activity may be orchestrated by secondary lymphoid organ-like aggregates residing in the tumor microenvironment. Known as tertiary lymphoid structures, these lymphoid aggregates serve as key outposts for lymphocyte recruitment, priming and activation. They have been linked to favorable outcomes in many tumor types, and more recently, have been shown to be effective predictors of response to immune checkpoint blockade. We have previously described a 12-chemokine (12-CK) transcriptional score which recapitulates an overwhelming enrichment for immune-related and inflammation-related genes in colorectal carcinoma. Subsequently, the 12-CK score was found to prognosticate favorable survival in multiple tumors types including melanoma, breast cancer, and bladder cancer. In the current study, we summarize the discovery and validation of the 12-CK score in various tumor types, its relationship to TLSs found within the tumor microenvironment, and explore its potential role as both a prognostic and predictive marker in the treatment of various cancers.

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