Prognostic roles for IL‐2‐producing and CD69⁺T cell subsets in colorectal cancer patients

Abstract

Tumor infiltrating T cells are a predictor of patient outcome in patients with colorectal cancer (CRC). However, many T cell populations have been associated with both poor and positive patient prognoses, indicating a need to further understand the role of different T cell subsets in CRC. In this study, the T cell infiltrate from the tumor and nontumor bowel (NTB) was examined in 95 CRC patients using flow cytometry and associations with cancer stage and disease recurrence made. Our findings showed that IFN-γ-producing T cells were associated with positive patient outcomes, and CD69 T cells were associated with disease recurrence. Inflammatory (IL-17) and regulatory T cells were not associated with disease recurrence. Surprisingly, in a second cohort of 32 patients with long-term clinical follow up data, tumor infiltrating IL-2-producing T cells correlated negatively with disease free survival (DFS) and a higher frequency of IL-2-producing T cells was found in the NTB of patients with poorly differentiated tumors. These results point toward the possibility of a negative impact of IL-2 in tumor immune responses, which may influence future immunotherapy treatments in CRC patients.

Association of serum interleukin-2 with severity and prognosis of community-acquired pneumonia: a prospective cohort study

“…High expression of IL-2 is positively correlated with the survival period of multiple myeloma patients [38]. The presence of IL-2 exacerbates the poor prognosis of colorectal cancer patients [39]. When IL-2 is elevated in patients diagnosed with non-Hodgkin lymphoma, their survival rates are diminished [40].…”

Identification of differentially expressed genes and enriched pathways in inflammatory bowel disease using bioinformatics and next generation sequencing data analysis

“…Signaling pathways include GPCR ligand binding [58], signaling by GPCR [59], signal transduction [60], GPCR downstream signaling [61], immune system [62], hemostasis [63], neutrophil degranulation [64], infectious disease [65] and neuronal system [66] were responsible for progression of IBD. GPR15 [67], ZNF365 [68], IL2 [69], IGFBP3 [70], FASLG (Fas ligand) [71], BTNL2 [72], S100B [73], FAP (fibroblast ABCA5 [220], DAB1 [221], SPRY2 [222], ANXA1 [223], MTSS1 [224], CCR6 [225], PTPRB (protein tyrosine phosphatase receptor type B) [226], SLC4A4 [227], PTCH1 [228], IL9R [229], PCDH9 [230], GAS1 [231], SELE (selectin E) [232], GZMA (granzyme A) [233], GZMB (granzyme B) [234], EMP1 [235], ABCB4 [236], LGALS4 [237], CD69 [238], BTLA (B and T lymphocyte associated) [239], ARHGEF28 [240], RGMB (repulsive guidance molecule BMP co-receptor b) [241], GPR63 [242], CXCL5 [243], HNF4A [244], BATF2 [245], SYT7 [246], GCKR (glucokinase regulator) [247], IGF2 [248], SDC1 [249], IGHG1 [250], MMP9 [251], PRKCG (protein kinase C gamma) [252], HP (haptoglobin) [253], GDF15 [254], GPR84 [255], S100A12 [256], ANXA3 [257], CBS (cystathionine beta-synthase)…”

Brick plots: an intuitive platform for visualizing multiparametric immunophenotyped cell clusters

“…CRC tissue samples were processed as described [20,21]. Briefly, samples were collected and digested prior to mechanical dissociation.…”

“…For the CRC cohorts, mass cytometry samples and flow cytometry samples were incubated with antibodies and processed as previously described [20,21]. For mass cytometry, all reagents were provided by the Ramaciotti Centre for Human Systems Biology, at the University of Sydney.…”

“…For flow cytometry, samples were incubated with a live/dead viability dye and incubated with fluorescently labelled antibodies [21] (Additional file 6).…”