GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in early-stage colorectal tumors and predict poor clinical outcome

• DOI: 10.1101/2021.12.14.472046
• Publication Date: 2021-12-15T19:55:12Z
• Authors: Silvia Tiberti; Carlotta Catozzi; Caterina Scirgolea; Ottavio Croci; Mattia Ballerini; Danilo Cagnina; Chiara Soriani; Carina B. Nava La...; Angeli D. Macandog; Giovanni Bertalot; Wanda L. Petz; Simona P. Ravenda; Valerio Licursi; Paola Paci; Marco Rasponi; Nicola Fazio; Guangwen Ren; Uberto Fumagalli-...; Martin H. Shaefer; Stefano Campaner; Enrico Lugli; Luigi Nezi; Teresa Manzo
• Keywords: Tumor-infiltrating lymphocytes

ABSTRACT Tumor contexture has emerged as a major prognostic determinant and tumor infiltrating CD8 + T cells have been associated with better prognosis in several solid tumors, including early-stage colorectal cancer (CRC). However, the immune infiltrate is highly heterogeneous understanding how interplay between different cell compartments impacts on clinical outcome still its infancy. Here, we describe prospective cohort novel effector memory population, which characterized by high levels of Granzyme K (GZMK EM ) correlated CD15 neutrophils. We provide both vitro vivo evidence role stromal cell-derived factor 1 (CXCL12/SDF-1) driving functional changes neutrophils at site, promoting their retention increasing crosstalk cells. Mechanistically, consequence interaction neutrophils, are skewed towards phenotype produce GZMK, turn decreases E-cadherin pathway. The correlations GZMK progression mice early relapse CRC patients demonstrate malignancy. Indeed, gene signature defining was worse larger independent similar analysis extended to lung (TCGA). Overall, our results highlight emergence tumors hallmark driven could implement current patient stratification be targeted therapeutics.