Figure 10.
Cross-presenting CD103+ DCs are critical for immune control of Ccr2−/− cancer cells. (A) Conditioned medium from Ccr2−/− cancer cells induces similar numbers of CD11c DCs (left) but more CD103+ BMDCs (right) in vitro compared with conditioned medium from Ccr2+/+ cancer cells (n = 3). (B) Conditioned medium from Ccr2+/+ cancer cells cultured with CCR2 inhibitor (inh.) induced similar numbers of CD11c DCs (left) but more CD103+ BMDCs (right) in vitro than conditioned medium from control cells cultured in the absence of the inhibitor medium (n = 3). (C) Tumors from transplanted Ccr2−/− cancer cells have elevated Csf2 mRNA (coding GM-CSF) and Flt3l (coding FLT3 ligand) but not Ccl2 or Csf3 compared with tumors from Ccr2+/+ cancer cells. RT-qPCR on tumors from transplanted Ccr2+/+ and Ccr2−/− cancer cells during the growth-restricted phase (n = 5 or 6 for Ccr2+/+ tumors, and n = 6 for Ccr2−/− tumors). (D) Tumor growth is increased in Batf3−/− hosts transplanted with Ccr2−/− cancer cells, as determined by weekly caliper measurements (n = 9 in Ccr2+/+ to Batf3−/− hosts group, and n = 10 for the other three groups). (E) CD103+ DCs are increased in Ccr2−/− tumors compared with Ccr2+/+ tumors in C57BL/6 hosts but are low in Batf3−/− hosts (n = 5). (F) CD8a+ T cells are increased in early-stage tumors (3 wk) from transplanted Ccr2−/− cancer cells compared with tumors from Ccr2+/+ cancer cells in C57BL/6 hosts but are low in Batf3−/− hosts (n = 9 or 10). (G) Lamp-1 (CD107a) and CD8a double-positive T cells are increased in early-stage tumors (3 wk) from transplanted Ccr2−/− cancer cells compared with tumors from Ccr2+/+ cancer cells but are low in Batf3−/− hosts (n = 9 or 10). (H) PD-1 and CD8a double-positive T cells are increased in early-stage tumors (3 wk) from transplanted Ccr2−/− cancer cells compared with tumors from Ccr2+/+ cancer cells in C57BL/6 hosts but are low in Batf3−/− hosts (n = 5). Means ± SEM are indicated. P values were determined by Student’s t test (A–C and E–H) or one-way ANOVA, followed by Sidak's multiple comparisons test at the end time point (D). *, P < 0.05; **, P < 0.01; ***, P < 0.001. N.S., nonsignificant.

Cross-presenting CD103+ DCs are critical for immune control of Ccr2 −/− cancer cells. (A) Conditioned medium from Ccr2−/− cancer cells induces similar numbers of CD11c DCs (left) but more CD103+ BMDCs (right) in vitro compared with conditioned medium from Ccr2+/+ cancer cells (n = 3). (B) Conditioned medium from Ccr2+/+ cancer cells cultured with CCR2 inhibitor (inh.) induced similar numbers of CD11c DCs (left) but more CD103+ BMDCs (right) in vitro than conditioned medium from control cells cultured in the absence of the inhibitor medium (n = 3). (C) Tumors from transplanted Ccr2−/− cancer cells have elevated Csf2 mRNA (coding GM-CSF) and Flt3l (coding FLT3 ligand) but not Ccl2 or Csf3 compared with tumors from Ccr2+/+ cancer cells. RT-qPCR on tumors from transplanted Ccr2+/+ and Ccr2−/− cancer cells during the growth-restricted phase (n = 5 or 6 for Ccr2+/+ tumors, and n = 6 for Ccr2−/− tumors). (D) Tumor growth is increased in Batf3−/− hosts transplanted with Ccr2−/− cancer cells, as determined by weekly caliper measurements (n = 9 in Ccr2+/+ to Batf3−/− hosts group, and n = 10 for the other three groups). (E) CD103+ DCs are increased in Ccr2−/− tumors compared with Ccr2+/+ tumors in C57BL/6 hosts but are low in Batf3−/− hosts (n = 5). (F) CD8a+ T cells are increased in early-stage tumors (3 wk) from transplanted Ccr2−/− cancer cells compared with tumors from Ccr2+/+ cancer cells in C57BL/6 hosts but are low in Batf3−/− hosts (n = 9 or 10). (G) Lamp-1 (CD107a) and CD8a double-positive T cells are increased in early-stage tumors (3 wk) from transplanted Ccr2−/− cancer cells compared with tumors from Ccr2+/+ cancer cells but are low in Batf3−/− hosts (n = 9 or 10). (H) PD-1 and CD8a double-positive T cells are increased in early-stage tumors (3 wk) from transplanted Ccr2−/− cancer cells compared with tumors from Ccr2+/+ cancer cells in C57BL/6 hosts but are low in Batf3−/− hosts (n = 5). Means ± SEM are indicated. P values were determined by Student’s t test (A–C and E–H) or one-way ANOVA, followed by Sidak's multiple comparisons test at the end time point (D). *, P < 0.05; **, P < 0.01; ***, P < 0.001. N.S., nonsignificant.

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