Treatment with molecular targeted agents together with
immune checkpoint inhibitors will most likely improve the efficacy of current
cancer immunotherapy. Because molecular targeted agents not only directly affect
cancer cells, but also influence immune cells and modulate the tumor microenvironment, a better understanding of the overall immunological effects of these drugs will contribute to the rational design of combination
therapies. Therefore, this study performed extensive immune monitoring of patients' peripheral blood mononuclear cells (PBMCs) to investigate the immunological effects of the molecular targeted agents
sunitinib,
everolimus and
temsirolimus, which have been widely used for the treatment of
renal cell carcinoma (RCC). Immunophenotyping and functional analysis of PBMCs revealed that these molecular targeted agents exerted different immunological effects on patients with RCC.
Sunitinib decreased the percentage of early‑stage myeloid‑derived suppressor cells (eMDSCs) and increased natural killer cells, but did not affect the phenotypes and effector functions of CD4+ or CD8+ T cells.
Everolimus decreased effector regulatory T cells, but also decreased IL‑2‑producing CD4+ T cells and increased dysfunctional CD8+ T cells. Conversely,
temsirolimus decreased
programmed cell death protein 1+CD8+ T cells and eMDSCs, but increased interferon‑γ and
tumor necrosis factor‑α double producers at the same time as decreasing dysfunctional CD8+ T cells, albeit not significantly. In conclusion, although
everolimus and
temsirolimus are
mTOR inhibitors, their effects on overall T‑cell functions are very different. Therefore, although it may increase the risk of immune‑related toxicity,
temsirolimus is expected to offer the best outcome when combined with other
immunomodulators for the development of
cancer immunotherapy.