TY - JOUR
T1 - Immunological effects of everolimus in patients with metastatic renal cell cancer
AU - Huijts, Charlotte M.
AU - Santegoets, Saskia J.
AU - de Jong, Tamarah D.
AU - Verheul, Henk M.
AU - de Gruijl, Tanja D.
AU - van der Vliet, Hans J.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - The mammalian target of rapamycin (mTOR) is a crucial kinase present in all cells. Besides its role in the regulation of cell-growth, proliferation, angiogenesis, and survival of malignant tumors, mTOR additionally plays an important role in immune regulation by controlling the balance between effector T cells and regulatory T cells (Tregs). This critically affects the suppressive state of the immune system. Here, the systemic immunological effects of everolimus treatment were comprehensively investigated in five patients with metastatic renal cell cancer. In this hypothesis generating study, the immunological alterations in circulating immune subsets induced by everolimus included a (non-significant) increase in the frequency of Tregs, a significant increase in monocytic myeloid-derived suppressor cells, a significant decrease in the frequency of immunoregulatory natural killer cells, classical CD141+ (cDC1) and CD1c+ (cDC2) dendritic cell subsets, as well as a decrease in the activation status of plasmacytoid dendritic cells and cDC1. These date indicate that the immunological effects of everolimus affect multiple immune cell subsets and altogether tip the balance in favor of immunosuppression, which can be considered a detrimental effect in the treatment of cancer, and may require combination treatment with agents able to negate immune suppression and boost T cell immunity.
AB - The mammalian target of rapamycin (mTOR) is a crucial kinase present in all cells. Besides its role in the regulation of cell-growth, proliferation, angiogenesis, and survival of malignant tumors, mTOR additionally plays an important role in immune regulation by controlling the balance between effector T cells and regulatory T cells (Tregs). This critically affects the suppressive state of the immune system. Here, the systemic immunological effects of everolimus treatment were comprehensively investigated in five patients with metastatic renal cell cancer. In this hypothesis generating study, the immunological alterations in circulating immune subsets induced by everolimus included a (non-significant) increase in the frequency of Tregs, a significant increase in monocytic myeloid-derived suppressor cells, a significant decrease in the frequency of immunoregulatory natural killer cells, classical CD141+ (cDC1) and CD1c+ (cDC2) dendritic cell subsets, as well as a decrease in the activation status of plasmacytoid dendritic cells and cDC1. These date indicate that the immunological effects of everolimus affect multiple immune cell subsets and altogether tip the balance in favor of immunosuppression, which can be considered a detrimental effect in the treatment of cancer, and may require combination treatment with agents able to negate immune suppression and boost T cell immunity.
KW - Treg
KW - everolimus
KW - immune monitoring
KW - mTOR
KW - suppression
UR - http://www.scopus.com/inward/record.url?scp=85039850605&partnerID=8YFLogxK
U2 - https://doi.org/10.1177/0394632017734459
DO - https://doi.org/10.1177/0394632017734459
M3 - Article
C2 - 28988508
SN - 0394-6320
VL - 30
SP - 341
EP - 352
JO - International journal of immunopathology and pharmacology
JF - International journal of immunopathology and pharmacology
IS - 4
ER -