Immunecheckpoint inhibitors such as Pembrolizumab, nivolumab (anti-PD-L1 agents) and Ipilimumab (anti-CTLA4 antibody) can cause myocarditis as the side effect. The same T cell clone population is expected to exist both in the tumor and the heart tissue which responds and exhibits the proliferation upon the exposure to the similar epitope. However, why other organs are spared and the heart tissue tend to harbor such epitope as to cause myocarditis?
My understanding of this peculiar phenomenon of T-cell-mediated immune reaction is that prolific T-cells were activated to target on certain common antigen shared by tumor cells and striated muscle including cardiac and skeletal muscles.
As Dr. Victor says, it is likely that the same antigen or the antigen with the same epitope exists both in the heart and tumor tissues.
It is important to identify the bona fide antigen with the same epitope between metastatic melanoma cells and striated muscles (heart and skeletal muscle). The identical T cell clone population is considered to expand due to the cross-talk. For instance, we have to rule out the possibility whether metastatic melanoma exhibits the expression of the protein, the epitope of which is the same as desmin.ab-crystallin etc.
Article Fulminant Myocarditis with Combination Immune Checkpoint Blockade
I agree with Victor and Go. In fact myocarditis is acompanied by general miositis. regards
Why smooth muscle was spared from the inflammation after the treatment with anti-PD-L1 antibody and/or anti-CTLA4 antibody for metastatic melanoma in the case report published by NEJM this week?
Article Fulminant Myocarditis with Combination Immune Checkpoint Blockade