Multiparametric analysis of CD8+ T cell compartment phenotype in chronic lymphocytic leukemia reveals a signature associated with progression toward therapy

Oncoimmunology. 2019 Feb 7;8(4):e1570774. doi: 10.1080/2162402X.2019.1570774. eCollection 2019.

Abstract

CD8+ T cells are frontline defenders against cancer and primary targets of current immunotherapies. In CLL, specific functional alterations have been described in circulating CD8+ T cells, yet a global view of the CD8+ T cell compartment phenotype and of its real impact on disease progression is presently elusive. We developed a multidimensional statistical analysis of CD8+ T cell phenotypic marker expression based on whole blood multi-color flow-cytometry. The analysis comprises both unsupervised statistics (hClust and PCA) and supervised classification methods (Random forest, Adaboost algorithm, Decision tree learning and logistic regression) and allows to cluster patients by comparing multiple phenotypic markers expressed by CD8+ T cells. Our results reveal a global CD8+ T cell phenotypic signature in CLL patients that is significantly modified when compared to healthy donors. We also uncover a CD8+ T cell signature characteristic of patients evolving toward therapy within 6 months after phenotyping. The unbiased, not predetermined and multimodal approach highlights a prominent role of the memory compartment in the prognostic signature. The analysis also reveals that imbalance of the central/effector memory compartment in CD8+ T cells can occur irrespectively of the elapsed time after diagnosis. Taken together our results indicate that, in CLL patients, CD8+ T cell phenotype is imprinted by disease clinical progression and reveal that CD8+ T cell memory compartment alteration is not only a hallmark of CLL disease but also a signature of disease evolution toward the need for therapy.

Keywords: CD8+ T cells; chronic lymphocytic leukemia; multidimensional phenotyping; phenotypic signature; supervised learning.

Publication types

  • Research Support, Non-U.S. Gov't

Grant support

This work was supported by the Institut National du Cancer under contracts INCa PBLIO11-130 and INCa/DGOS 2012-054; Region Occitanie under contracts RCLE R14007BB, No 12052802, and RBIO R15070BB, No 14054342; the Laboratoire d’Excellence Toulouse Cancer (TOUCAN) under contract ANR11-LABX; Fondation Toulouse Cancer Santé under contract 2014CS044 and Ligue Nationale contre le Cancer (Equipe labellisée 2018). P.G. was supported by INCa, Region Occitanie and Fondation Toulouse Cancer Santé. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.