Abstract
The multikinase inhibitors sunitinib, sorafenib, and axitinib have an impact not only on tumor growth and angiogenesis, but also on the activity and function of immune effector cells. In this study, a comparative analysis of the growth inhibitory properties and apoptosis induction potentials of tyrosine kinase inhibitors on T cells was performed. Tyrosine kinase inhibitor treatment resulted in a dramatic decrease in T cell proliferation along with distinct impacts on the cell cycle progression. This was at least partially associated with an enhanced induction of apoptosis although triggered by distinct apoptotic mechanisms. In contrast to sunitinib and sorafenib, axitinib did not affect the mitochondrial membrane potential (Δψm) but resulted in an induction or stabilization of the induced myeloid leukemia cell differentiation protein (Mcl-1), leading to an irreversible arrest in the G2/M cell cycle phase and delayed apoptosis. Furthermore, the sorafenib-mediated suppression of immune effector cells, in particular the reduction of the CD8+ T cell subset along with the down-regulation of key immune cell markers such as chemokine CC motif receptor 7 (CCR7), CD26, CD69, CD25, and CXCR3, was not observed in axitinib-treated immune effector cells. Therefore, axitinib rather than sorafenib seems to be suitable for implementation in complex treatment regimens of cancer patients including immunotherapy.
Keywords: Apoptosis, Immunology, Immunosuppression, Immunotherapy, T Cell, Axitinib, Sorafenib, Sunitinib, Targeted Therapy, Tyrosine Kinase Inhibitor
https://www.ncbi.nlm.nih.gov/pmc/articl ... po=72.8723
Reduced Immunosuppressive Properties of Axitinib in Comparison with Other Tyrosine Kinase Inhibitors*
Re: Reduced Immunosuppressive Properties of Axitinib in Comparison with Other Tyrosine Kinase Inhibitors*
Thank you Deb, very interesting indeed.
I didn't know that Tyrosine kinase inhibitor treatment cause a decrease in T cell proliferation. Perhaps instead of testing the combination trial in ASPS, they should have started from the ICI drugs alone. Otherwise they never know if the combination is really more effective than the drug alone. Although it is good to hear that at least Axitinib is less immunosupressive.
I didn't know that Tyrosine kinase inhibitor treatment cause a decrease in T cell proliferation. Perhaps instead of testing the combination trial in ASPS, they should have started from the ICI drugs alone. Otherwise they never know if the combination is really more effective than the drug alone. Although it is good to hear that at least Axitinib is less immunosupressive.
Olga
Re: Reduced Immunosuppressive Properties of Axitinib in Comparison with Other Tyrosine Kinase Inhibitors*
Indeed Olga.
Myself included not knowing .😏
With the advent of TKIs , they have helped lots of our folks . So my thought is don’t throw them aside especially when we are on the brink of success with ICIs.
This thought was opened for discussion at our appointment today .👍🏼
Through my research and observation of re occurrence in our fellow ASPS folks , it’s come to my attention that because of immune suppressive situations Ie Surgeries , treatments , added meds maybe a big player in these reoccurrences .
Also I’ve noticed that pregnancies have been linked to either early concurrent or later reoccurrence , of folks developing ASPS. Hormone and immune suppression of the women’s body during this wonderment. Possibly the dx’d age of youngmen?
Good info to know in our fight to make ASPS just a chronic disease .
Love to all,
Myself included not knowing .😏
With the advent of TKIs , they have helped lots of our folks . So my thought is don’t throw them aside especially when we are on the brink of success with ICIs.
This thought was opened for discussion at our appointment today .👍🏼
Through my research and observation of re occurrence in our fellow ASPS folks , it’s come to my attention that because of immune suppressive situations Ie Surgeries , treatments , added meds maybe a big player in these reoccurrences .
Also I’ve noticed that pregnancies have been linked to either early concurrent or later reoccurrence , of folks developing ASPS. Hormone and immune suppression of the women’s body during this wonderment. Possibly the dx’d age of youngmen?
Good info to know in our fight to make ASPS just a chronic disease .
Love to all,
Debbie