Fig. 1
Tumor-associated inflammatory infiltrate, systemic inflammatory response and therapeutic response in the discovery set of mCRC. a Tumor-associated quantification of individual cell types, CD3+ T cells, CD68+ monocyte-macrophage cells, CD15/FUT4+ neutrophils (n = 32) considering all tumor locations (invasive front, stroma and intraepithelial). One dot represents mean of five replicates cells counts, expressed as cells mm−2. Bars represent medians (200, 140 and 56.5 cells counts, respectively). b Clustering analysis according to the patients’ best response to first line therapy. Interrelationship among, quantification of four types of inflammatory cells, systemic inflammatory response (NLR at time of diagnosis), tumor-related expression of immune markers including (CD73) and KRAS mutational status in each patient of the discovery set. Tumor infiltrating immune-cells include an additional one, MPO+ for neutrophils granulocytes). Immune-positivity on malignant cells is expressed as negative (green), low (blue) and high (red) (see methods for score details). Of note, all patients progressing to first line therapy overexpressed CD15/FUT4 on cancer cells. c Representative pictures for CD15/FUT4 IHC in normal mucosae and tumor specimens, respectively. CD15/FUT4 marks intensely neutrophils granulocytes (red arrows) but not or weakly colonic epithelial cells in normal mucosa (black arrow). Cancer-related CD15/FUT4 expression pattern detected in tumors: red arrows indicates stromal compartment, black arrows indicate malignant cells. d Relationship between cancer-relatedCD15/FUT4 expression pattern (negative, low and high subgroups) and Progression-Free Survival (PFS) after first line therapy. Distribution of PFS expressed in months, into subgroup CD15/FUT4-high, low and negative tumors, respectively. Bars represent medians (13, 11 and 7.5 months, respectively). Abbreviations: neutrophil-to-lymphocyte ratio, NLR