Involvement of CD8 T cells in the tumor growth control and in the response to PD1 and PDL1 antibodies

However, while aiming at improving the rate of response to immunotherapeutic treatments and at promoting potential synergistic activities, it is increasingly crucial to understand the mechanisms underlying the antitumor activity of immunotherapeutic treatments. Hence, the elucidation of the contribution of immune subpopulations, such as effector or immunosuppressive cells, and understanding of which immune cell population(s) are involved in an anti-tumor effect would allow to improve the effectiveness of anti-cancer treatments and assess new potential combinatorial strategies.

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 (5×10⁵ 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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