Involvement of CD8 T cells in the tumor growth control and in the response to PD1 and PDL1 antibodies
09 / 12 / 2019
As case study presented here, we show that PD1 and PDL1 blockade promote strong antitumor effects in the syngeneic MCA205 sarcoma bearing tumor model, and that CD8 T cells play an unequivocal role in this antitumor activity.
Figure 1. Effects of CD8 depletion in vehicle and PD1/PDL1 blockade treated MCA205 tumor-bearing mice (5x105 cells). (A) CD8 depletion facilitated tumor outgrowth compared to control (isotype treated) group, thereby underlining the crucial role of CD8 T cells in mediating tumor growth control. (B & C) While PD1 and PDL1 blockade antibodies displayed a pronounced antitumor activity, their effects were completely reversed under CD8 depleting Ab treatment, showing that this antitumor activity is mainly CD8 T cell-driven.
Figure 2. Effects of CD8 depletion in vehicle and PD1/PDL1 blockade treated MCA205 tumor-bearing mice (Individual tumor growth). CD8 depletion facilitated tumor outgrowth (Individual tumor volume) compared to control (isotype-treated) group (Left panel). The effects of anti-PD1 (Middle panel) or anti-PDL1 (Right panel) were completely reversed under CD8 depleting Ab treatment, showing that this antitumor activity is mainly CD8 T cell-driven.
Figure 3. Peripheral blood FACS profiling supports the efficiency of CD8 depletion. Flow cytometry monitoring of CD3, CD4, and CD8 cell populations in peripheral blood samples, 1 day and 2 weeks after the 1st injection of CD8 depleting Ab. CD8 depleting Ab produced an efficient and stable CD8 depletion concomitantly with a higher proportion of CD4 T cells.
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