Fig. 3: Elovl1-deficient CD8+ T cells have increased antitumoural activity upon anti-PD-1 treatment.

a,b, Tumour weight (a) and peritoneal metastasis count (b), on day14 post-KPC_OVA injection, of mice not treated (PBS), receiving sgNT or sgElovl1 OT-I T cells and treated with IgG or anti-PD-1. c, Representative haematoxylin and eosin picture of one lobe of the liver (scale bar, 2.5 mm, left) and percentage of tumour area (right) in an experimental model of PDAC liver metastasis. The mice were injected intrasplenic with KPC_OVA. Eight days later, they received sgNT or sgElovl1 OT-I T cells and started anti-PD-1 therapy the following day (n = 5). Tumour burden was quantified on every lobe and calculated as percentage of total area. d, Flow cytometry quantification of sgNT and sgElovl1 OT-I cells in the primary tumour of mice treated with IgG or anti-PD-1. e,f, Flow cytometry quantification of PD-1+ Tim3+ (e) and TNF+ IFNγ+ (f) percentage of sgNT and sgElovl1 OT-I cells infiltrating KPC_OVA primary tumour of mice treated with IgG or anti-PD-1. g, Representative flow cytometry histogram and quantification of IL-2 production (median of fluorescence intensity; MFI) of sgNT or sgElovl1 OT-I T cells infiltrating KPC_OVA primary tumour of mice treated with IgG or anti-PD-1. h–j, Flow cytometry quantification of Ki67 (h) and CD44+CD62L+ (Tcm) (i) in sgNT or sgElovl1 OT-I T cells infiltrating the spleen and CD44+ CD62L+ (Tcm) in sgNT or sgElovl1 OT-I cells infiltrating the draining lymph nodes (j) of KPC_OVA-bearing mice treated with IgG or anti-PD-1. k, Representative tumour growth curve of mice injected subcutaneously with B16F1 cells and treated with anti-PD-1 that received sgNT or sgElovl1 pmel-1 T cells (sgNT n = 8; sgElovl1 n = 5). l, Tumour weight of B16F1 tumour-bearing mice injected with sgNT or sgElovl1 pmel-1 cells (sgNT n = 12, sgElovl1 n = 11). m,n, Flow cytometry quantification of IFNγ+ (m) and Ki67+ (n) pmel-1 T cells infiltrating B16F1 primary tumour (sgNT n = 8, sgElovl1 n = 5). o, Flow cytometry quantification of PD-1+ Slamf6+ (Tpex) pmel-1 T cells infiltrating B16F1 primary tumour (sgNT n = 11, sgElovl1 n = 7). (a,b,f,g,I,j, sgNT + IgG, n = 10; sgElovl1 + IgG, n = 10, sgNT + anti-PD-1, n = 10; sgElovl1 + anti-PD-1, n = 10, two independent experiments). (e,h, sgNT + IgG, n = 5; sgElovl1 + IgG, n = 5, sgNT+ anti-PD-1, n = 5; sgElovl1 + anti-PD-1, n = 5). Data are presented as mean ± s.e.m. Statistical significance was assessed by one-way (a,b,d–j) or two-way (k) ANOVA and by two-tailed unpaired Student’s t-test (c,l–o).