Figure 6.

Cooccurrence of FLT3LG expression and the CCL5 associates with increased conventional type 1 dendritic cell (cDC1) score and better survival in several human cancers. (A) Correlation of FLT3LG and CCL5 expression within tumors of metastatic skin cutaneous melanoma (M-SKCM), breast carcinoma (BRCA) and cervical squamous carcinoma (CESC) using data extracted from the The Cancer Genome Atlas. Patients with cancer were assigned an FLT3LG/CCL5 score and sorted into low (first quartile), intermediate (second and third quartiles) and high (fourth quartile). (B) cDC1 score based on expression of KIT, CCR7, BATF3, FLT3, ZBTB46, IRF8, BTLA and MYCL1 as explained in Methods was calculated within tumors from the quartile subcohorts of patients with M-SKCM, BRCA and CESC. (C) Overall survival of the quartile subcohorts of patients indicated in (A). (D–F) B16F10 tumor-bearing WT mice were inoculated with cyclophosphamide (CTX) at days 8 and 14 of tumor development. (D) At day 16, blood was collected and serum levels of FLT3L were quantified. (E, F) B16F10 tumors were inoculated in the flank of WT and Clec9a^gfp/gfp mice, which were treated with CTX at days 8 and 14. The graphs represent the tumor growth curves (E) and survival curves (F). (A) Each point indicates a patient. r, Pearson correlation coefficient. (B) Whisker plot of cDC1 score for patients with cancer was calculated based on the expression of KIT, CCR7, BATF3, FLT3, ZBTB46, IRF8, BTLA and MYCL1. Statistical significance was assessed by one-way analysis of variance (ANOVA) followed by Fisher’s least significant difference test. (D) Graph shows the mean of one experiment where each dot represents one mouse. (E, F) These graphs contain a pool of two independent experiments with n=6 for untreated mice, n=11 for WT + CTX and n=14 for Clec9a^gfp/gfp + CTX. Statistical significance was evaluated by pairwise Mantel-Cox test (C, F), Student’s t-test (D) and two-way ANOVA (E). *p<0.05 and ***p<0.001.