Importantly, absence of Cbl-b could also render T cells resistant to the tolerogenic tumor microenvironment, since T cells from Cbl-b−/− mice cannot be anergized, neither in vitro upon incubation with ionomycin nor in vivo, in P14 or OTII TCR transgenic mouse models of anergy [132,133], and are resistant to Treg and TGF-β suppression [125,126,134] well as to PD-1 or CTLA-4 inhibition [135,136]. The gene discussed is PDCD1; the disease is neoplasm.