Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer.
By M. Tosolini, A. Kirilovsky, Bernhard Mlecnik, T. Fredriksen, Stéphanie Mauger, Gabriela Bindea, A. Berger, P. Bruneval, W. Fridman, Franck Pagès and 1 more. Cancer Research, 2011
1,129 citations recorded by the source corpus.
The tumor microenvironment includes a complex network of immune T-cell subpopulations. In this study, we systematically analyzed the balance between cytotoxic T cells and different subsets of helper T cells in human colorectal cancers and we correlated their impact on disease-free survival. A panel of immune related genes were analyzed in 125 frozen colorectal tumor specimens. Infiltrating cytotoxic T cells, Treg, Th1, and Th17 cells were also quantified in the center and the invasive margin of the tumors. By hierarchical clustering of a correlation matrix we identified functional clusters of genes associated with Th17 (RORC, IL17A), Th2 (IL4, IL5, IL13), Th1 (Tbet, IRF1, IL12Rb2, STAT4), and cytotoxicity (GNLY, GZMB, PRF1). Patients with high expression of the Th17 cluster had a poor prognosis, whereas patients with high expression of the Th1 cluster had prolonged disease-free survival. In contrast, none of the Th2 clusters were predictive of prognosis. Combined analysis of cytotoxic/Th1 and Th17 clusters improved the ability to discriminate relapse. In situ analysis of the density of IL17+ cells and CD8+ cells in tumor tissues confirmed the results. Our findings argue that functional Th1 and Th17 clusters yield opposite effects on patient survival in colorectal cancer, and they provide complementary information that may improve prognosis.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/60c45e15e87842d0e3b5c25493e4d2d34dab9a2d
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Citations in the corpus
- The IL-17 family of cytokines in health and disease (2019, background): “For many tumor types, particularly at mucosal barriers, gene signatures of Th1 cells (IFNG, STAT1, TBX21) and CD8+ cytotoxic T cells (PRF1, GZMB) are linked to better overall and relapse-free patient survival, whereas Th17 cell signatures (RORC, IL17, IL23, STAT3) correspond to worse patient outcome”
- The Consensus Molecular Subtypes of Colorectal Cancer (2015, methodology): “is supported by grants from the Dutch Cancer Society (UVA2011-4969, UVA2014-7245), Worldwide Cancer Research (14-1164), the Maag Lever Darm Stichting (MLDS-CDG 14-03) and the European Research Council (ERG-StG 638193).”
- Roles of the immune system in cancer: from tumor initiation to metastatic progression (2018, background): “Notably, HLA loss has been associated with resistance to T-cell transfer therapy in metastatic colorectal cancer (Tran et al. 2016) and poor outcome response to checkpoint blockade immuno-therapy in melanoma and lung cancer patients (Chowell et al. 2018).”
- Immunity, inflammation, and cancer: an eternal fight between good and evil. (2015, positive): “Furthermore, elevated expression of IL-17A and IL-23R in stage I and II human CRC correlates with rapid progression to lethal metastatic disease (36).”
- Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours (2013, background): “Accumulat-ing evidence suggests that CD3+ [9,10,30,34,37–43], CD8+ [9,10,34,38,43–52] and CD45RO+ [9,10,34,40,47,49,53,54] cells have roles in antitumour immune responses.”
- OMIP‐050: A 28‐color/30‐parameter Fluorescence Flow Cytometry Panel to Enumerate and Characterize Cells Expressing a Wide Array of Immune Checkpoint Molecules (2018, background): “Notably, the frequency of certain memory subsets, such as central memory (Tcm) and T helper type 1 (Th1), has been associated with clinical benefits (11).”
- Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “Presence of certain chemokines, cytokines and myeloid cell subsets correlate with poor prognosis in CRC, as established in the “CRC immunoscore” by the Galon group (Mlecnik et al., 2016; Tosolini et al., 2011), which most likely will be further modified and expanded for other tumor types as well.”