Supporting Cases for the Depletion Model of Immune Check pointInhibitor Therapy in Cancer

Abstract

Immune checkpoint inhibitor therapy has been introduced into cancer clinics for over a decade with big hopes and hypes, yet the true mechanism behind this therapy is still unclear in many ways. In a previous article we have introduced a new working model for this therapy based on the partial depletion of PD1 positive T cells. This model, as we called it the depletion model, explains all clinical observations including the trigger effect and the hyper- rogression associated with anti-PD1/PDL1 antibody use. One critical prediction from this model is that under repeated dosing of anti-PD1 antibody, any antitumor response must be mediated by PD1-negative T cells, because that all PD1-positive T cells are removed by the antibody. Unless this prediction can be confirmed, the depletion model will not be supported by evidence. In this report, using few real-world cases, we provide supporting evidence to support the various aspects of the depletion model.