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Chemotherapy Combines Effectively with Anti-PD-L1 Treatment and Can Augment Antitumor Responses. | LitMetric

AI Article Synopsis

  • - The study investigates the effect of combining chemotherapy with checkpoint inhibitors, specifically anti-PD-L1, in a mouse model of cancer, finding that while chemotherapy generally reduces immune cell activity in the body, it can enhance the anti-tumor effects of anti-PD-L1 treatment.
  • - The researchers noted that the positive antitumor response often occurs despite chemotherapy's negative impact on immune cells outside of tumors, as established tumors rely less on new incoming immune cells for their control.
  • - Different chemotherapy agents can work alongside anti-PD-L1 through various mechanisms, supporting the idea that combining these therapies could lead to better cancer treatment outcomes, despite the overall immune suppression caused by chemotherapy.

Article Abstract

Immunotherapy with checkpoint inhibitors has proved to be highly effective, with durable responses in a subset of patients. Given their encouraging clinical activity, checkpoint inhibitors are increasingly being tested in clinical trials in combination with chemotherapy. In many instances, there is little understanding of how chemotherapy might influence the quality of the immune response generated by checkpoint inhibitors. In this study, we evaluated the impact of chemotherapy alone or in combination with anti-PD-L1 in a responsive syngeneic tumor model. Although multiple classes of chemotherapy treatment reduced immune cell numbers and activity in peripheral tissues, chemotherapy did not antagonize but in many cases augmented the antitumor activity mediated by anti-PD-L1. This dichotomy between the detrimental effects in peripheral tissues and enhanced antitumor activity was largely explained by the reduced dependence on incoming cells for antitumor efficacy in already established tumors. The effects of the various chemotherapies were also agent specific, and synergy with anti-PD-L1 was achieved by different mechanisms that ultimately helped establish a new threshold for response. These results rationalize the combination of chemotherapy with immunotherapy and suggest that, despite the negative systemic effects of chemotherapy, effective combinations can be obtained through distinct mechanisms acting within the tumor.

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Source
http://dx.doi.org/10.4049/jimmunol.1800275DOI Listing

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