Abstract 2050: Treatment with anti-PD-1 monoclonal antibody increases levels of MIP-1α and other cytokines, and suppresses tumor growth in a mouse model of triple negative breast cancer
Authors: Cruz Payton De La , Grive Kathryn , Ribeiro Jennifer 
Published: June 2022

Background: Triple negative breast cancer (TNBC), characterized by the lack of estrogen and progesterone receptors and HER2, is an aggressive form of breast cancer that accounts for 15-20% of all diagnosed cases. There are few targeted therapies available for TNBC, but immune checkpoint inhibitors (ICIs) such as Pembrolizumab have been shown to be effective in a subset of TNBC patients. However, because ICIs are rarely administered as a monotherapy, there remains little foundational understanding of how single-agent immunotherapies alter the immune landscape and which circulating immune profiles predict therapeutic response in TNBC. Therefore, further investigation into the distinct immune signatures of ICIs are necessary for developing a rational basis for selecting optimal treatment regimens for TNBC.

Methods: E0771 cells, a C57Bl/6 mouse-derived TNBC cell line, were injected into the bilateral mammary pads of 8 week old female C57Bl/6J mice. Control mice were injected with saline into mammary pads. After tumors developed (14 days post-implantation), E0771 mice received 200 ug doses of immunotherapy (anti-PD-1, anti-LAG-3, or anti-TIM-3 antibodies) or IgG isotype control every four days. After 3 doses, treatments were stopped and serum was collected from “on-treatment” mice. Fourteen days after the third treatment, serum was collected from “post-treatment” mice. A panel of 31 cytokines, chemokines, and growth factors were analyzed in “pre-treatment”, “on-treatment”, “post-treatment”, and saline control mouse serum using a BioPlex 200 multiplex system (Eve Technologies).

Results: Mice treated with anti-PD-1 antibody showed significantly higher levels of several cytokines and chemokines compared to isotype control mice. Among the most significantly increased cytokines in the post-treatment anti-PD-1 group was macrophage inflammatory protein-1α (MIP-1α), or CCL3. MIP-1α is a chemotactic cytokine secreted by several types of immune cells that is known to attract macrophages and CD8+ T cells. More subtle changes in levels of several cytokines, chemokines, and growth factors were observed in anti-LAG-3 and anti-TIM-3 treatment groups. At the post-treatment timepoint, mice treated with anti-PD-1 antibody had smaller tumor sizes than mice treated with anti-LAG-3 and anti-TIM-3 antibodies, indicating that PD-1 blockade slows tumor growth and disease progression.

Conclusion: Anti-PD-1 treatment induced more distinct circulating immune profiles and was more effective at controlling tumor growth than anti-LAG-3 and anti-TIM-3 treatments. These results may also suggest MIP-1α-mediated tumor regression in response to anti-PD-1 treatment in TNBC.

Citation Format: Payton De La Cruz, Kathryn Grive, Jennifer Ribeiro. Treatment with anti-PD-1 monoclonal antibody increases levels of MIP-1α and other cytokines, and suppresses tumor growth in a mouse model of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2050.