Mechanism underlying the immune checkpoint inhibitor-induced hyper-progressive state of cancer

Immune checkpoint inhibitors (ICIs) are gradually replacing chemotherapy as the cornerstone of the treatment of advanced malignant tumors because of their long-lasting and significant effect in different tumor types and greatly prolonging the survival time of patients. However, not all patients can respond to ICIs, and even rapid tumor growth after treatment with ICI has been observed in a number of clinical studies. This rapid progression phenomenon is called hyper-progressive disease (HPD). The occurrence of HPD is not uncommon. Past statistics show that the incidence of HPD is 4%-29% in different tumor types, and the progression-free survival and overall survival of patients with HPD are significantly shorter than those of the non-HPD progressor group. With the deepening of the study of HPD, we have established a preliminary understanding of HPD, but the diagnostic criteria of HPD are still not unified, and the addition of biomarkers may break this dilemma. In addition, quite a few immune cells have been found to be involved in the occurrence and development of HPD in the tumor microenvironment, indicating that the molecular mechanism of HPD may be triggered by a variety of ongoing events at the same time. In this review, we summarize past findings, including case reports, clinical trials, and fundamental research; compare the diagnostic criteria, incidence, and clinical prognostic indicators of HPD in different studies; and explore the molecular mechanism and future research direction of HPD.