Immunotherapy has shown great promise as a cancer treatment resulting in several FDA approved drugs and clinical trials. For example, a promising therapy in several tumors is the blocking of the PD-1/PD-L1 interaction that is over expressed on many types of tumor cells.  However, success depends on the patient’s immune system to respond to the tumor.

Immunotherapy is typically used in combination with other agents. The most common combination are chemotherapeutic agents, which are known for suppressing the immune system. These agents include tyrosine kinase inhibitors (TKIs). TKIs are used to treat several neoplastic diseases, most notably chronic myelogenous leukemia (CML).  To further examine the effect of TKIs on the immune system, Heine, et al., studied the effect of several TKIs on the induction of myeloid derived suppressor cells (MDSCs). MDSCs are negative regulators of the immune system that can accumulate in cancer patients.

In this study, researchers used a Sony SH800 cell sorter to isolate CD14+ cells (monocytes) and CD8+ T cells from healthy volunteers and patient samples. The monocytes were co-cultured with hepatic stellate cells (HSCs) to induce MDSCs. The co-cultures were exposed to several TKIs including: nilotinib, dasatinib, sorafenib, and sunitinib at different times points. Cells were characterized in several assays including apoptosis and immunophenotyping on the Sony SP6800 Spectral Analyzer. When the monocytes were treated with three out of the four agents, there was decrease the differentiation of monocytes into MDSCs.  T-cell suppression was also reduced.

These results suggest that the timing and choice of TKI can modulate the success of cancer immunotherapeutics. This study may be a useful model to examine the impact of other therapeutics on the immune system and the compatibility of those therapeutics with immune checkpoint inhibitors.

 

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References

Heine, A, et al. "The induction of human myeloid derived suppressor cells through hepatic stellate cells is dose-dependently inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib and sorafenib, but not sunitinib." Cancer Immunol Immunother. 65.3 (2016): 273-282. PubMed