Fig. 2: Chemotherapeutic agents, but not MEK inhibitors, impair T cell proliferation and activation in vivo. | Nature Communications

Fig. 2: Chemotherapeutic agents, but not MEK inhibitors, impair T cell proliferation and activation in vivo.

From: Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy

Fig. 2

a C57BL/6-Ly5.1 (CD45.1+) mice infused with CFSE-labeled OT-I T cells (CD45.2+) were treated for 6 days with the indicated doses of MEK inhibitor GDC-0623 or vehicle. Mice were immunized with OVA protein admixed with anti-CD40 Ab. After 3 days, splenocytes were analyzed. Upper row: dot plots of gated OT-I T cells. Lower row: CFSE dilution of gated OT-I T cells; differentially colored histograms represent data from individual mice. Bar charts to the right: cumulative data from six experiments (total mice: vehicle n = 23, GDC-0623 (10 mg kg−1) n = 19, GDC-0623 (30 mg kg−1) n = 21), showing quantification of OT-I T cell numbers and divided fraction. One-way ANOVA with post hoc Tukey’s test. Significance levels are indicated by asterisks (*p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001). b Intracellular IFNγ levels of OT-I T cells after ex vivo restimulation with SIINFEKL peptide. Bar charts to the right: cumulative data of four experiments (total n ≥ 12 mice per group). c CD45.1+ mice infused with naive CD45.2+ OT-I T cells were immunized with OVA protein admixed with anti-CD40 Ab. Three days later, mice were infused with CFSE-labeled peptide pulsed target cells (CD45.2+ splenocytes pulsed with 10 µg ml−1 SIINFEKL; 0.3 µm CFSE) admixed with control cells (CD45.2+ splenocytes pulsed with 10 µg ml−1 P53 control peptide AIYKKSQHM; 5 µm CFSE); spleens were analyzed for target cell killing after 24 h. GDC-0623 was administered at indicated doses for 3 days after immunization. Bar charts to the right: cumulative data of two experiments (vehicle n = 8, GDC-0623 (10 mg kg−1) n = 6, GDC-0623 (30 mg kg−1) n = 6) with specific killing normalized to the T cell only group. d As described in a, mice were treated on days 0 and 3 with indicated doses of temozolomide (TEM), gemcitabine (GEM), or vehicle. Upper row: dot plots of gated OT-I T cells. Lower row: CFSE dilution of gated OT-I T cells. Bar charts to the right: quantification of OT-I T cell numbers and divided fraction (three mice/group).

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