Introduction:
Immune evasion is an important mechanism that can lead to uncontrolled proliferation and metastasis of tumor cells. To this end, natural control mechanisms such as immune checkpoints or immunosuppressive cells are exploited to weaken an anti-tumor immune response. The blockade of the checkpoint inhibitors already shows positive effects in cancer therapy. However, previous chemotherapy and the immune checkpoint blockade itself can lead to changes in the checkpoint expression, which influence the success of therapy.
Methods:
Multiple lymphocyte populations (B and T cells, regulatory T cells) from healthy donors were treated in vitro with different chemotherapeutic agents (cisplatin, methotrexate, 5-FU) or nivolumab. The expression of nine immune checkpoints and the production of intracellular cytokines (IL-2, INF-γ, TNF-α) were measured by flow cytometry.
Results:
After in vitro treatment with different chemotherapeutic agents, the lymphocyte populations showed altered immune checkpoint expression. Depending on the cytostatic drug, specific effects were found. In addition, following nivolumab treatment, a reduction in PD-1 expression at protein and mRNA levels as well as increased cytokine production could be demonstrated.
Conclusion. We demonstrated that chemotherapeutics have various effects on the regulation of specific immune checkpoints. These changes may affect the success of a subsequent immunotherapy and should therefore be considered.
