Figure 4.

Genetic Ablation of COX in Braf^V600E or Nras^G12D Melanoma Cells Enables Immune-Dependent Tumor Eradication

(A–C) Growth of tumors formed following implantation of 10⁵ control or Ptgs1/Ptgs2^−/− Braf^V600E cells into WT C57BL/6 (A–C), Rag1^−/− (A), Batf3^−/−, Tap1^−/− (B), or Ifnar1^−/− (C) mice.

(D) Growth of parental Braf^V600E cells following implantation into naive WT C57BL/6 mice or mice that previously rejected Ptgs1/Ptgs2^−/− Braf^V600E tumors (pre-inoculated). Data are compiled from three independent experiments and presented as tumor growth profile (left) and as percentage of tumor-free mice at 6 weeks post-parental tumor inoculation (right).

(E) Concentration of PGE₂ in CM from confluent parental or Pges^−/− cell cultures cells or of TNF and IL-6 in the supernatant of an overnight culture of BMMCs cultured as in Figure 1 in presence of CM from the indicated cell line and expressed as in Figure 1G.

(F) Growth profile of tumors formed following implantation of 10⁵ parental or Pges^−/− Braf^V600E cells into WT or Rag1^−/− mice.

(G) Concentration of PGE₂ in CM from confluent cell cultures or growth profile of tumors formed following implantation of 10⁵ parental or Ptgs2^−/− Nras^G12D cells into WT or Rag1^−/− mice (right). (H) The percentage of tumor-free mice at 6 weeks post-implantation of parental Nras^G12D cells into naive WT C57BL/6 mice or mice that previously rejected Ptgs2^−/− Nras^G12D tumors (pre-inoculated). All growth profiles are presented as average tumor diameters ± SEM and are representative of at least two independent experiments with four to six mice per group. Tumor growth profiles were compared using two-way ANOVA and the percentage of tumor-free mice using Fisher’s exact test. ^∗∗∗p < 0.001.

See also Figure S6.