ICOS and neoplasm: Due to the role of CTLA-4 in inhibiting T cell proliferation and the very high expression of PD-1 by Tfh cells and the aforementioned tumor-associated Tfh-like cells as well as Tph cells, it is tempting to speculate that ICI treatments such as anti-CTLA-4 as well as anti-PD-1 or anti-PD-L1 in the context of cancer immunotherapy may lead to further activation of these cells, which already express high levels of CD40L, ICOS and other co-stimulatory molecules, and thereby unleashing the generation of autoantibodies with tumor-unrelated antigen specificity.