Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity

Abstract

Immune checkpoint inhibitors provide considerable therapeutic benefit in a range of solid cancers as well as in a subgroup of hematological malignancies. Response rates are however suboptimal, and despite considerable efforts, predicting response to immune checkpoint inhibitors ahead of their administration in a given patient remains elusive. The study of the dynamics of the immune system and of the tumor under immune checkpoint blockade brought insight into the mechanisms of action of these therapeutic agents. Equally relevant are the mechanisms of adaptive resistance to immune checkpoint inhibitors that have been uncovered through this approach. In this review, we discuss the dynamics of the immune system and of the tumor under immune checkpoint blockade emanating from recent studies on animal models and humans. We will focus on mechanisms of action and of resistance conveying information predictive of therapeutic response.

Editorial: Dynamic Biomarkers of Response to Anti-Immune Checkpoint Inhibitors in Cancer

“…We have recently summarized the dynamics of the immune system and of the tumor under immune checkpoint blockade. We emphasized the importance of studying mechanisms influencing response to ICB and focused on the multitude of immune cells subsets (including effector and immunosuppressive T cells and B cells subsets) that were shown to be impacted by CTLA-4 and PD-1/PD-L1 blockade monotherapy ( 3 ). In this Research Topic, we compiled reviews and original research articles reflecting the current advances in the study of dynamic biomarkers as predictors of the response to checkpoint inhibitors therapies in cancer.…”

Prediction of Early Response to Immunotherapy: DCE-US as a New Biomarker

“…This result seems to be consistent with the changes in the tissue level induced by the introduction of ICIs. Immune checkpoint blocking is shown to activate and lead to the proliferation of T-cells and NK-cells [ 15 , 19 ]. A pro-inflammatory environment is created.…”

“…This technique brings to light the inflammation process induced by ICI and observes the tumor destruction by the immune system. After ICI administration, a lymphoproliferation is observed, resulting in an influx of immune cells [ 15 ], leading to an increase of perfusion followed by a decrease due to necrosis induced by the destruction of tumor cells and vasculature. Our study aims to determine whether perfusion parameters extracted from dynamic contrast-enhanced ultrasound can be used as biomarkers for ICI early response evaluation.…”

Regulation of the innate immune cells during pregnancy: An immune checkpoint perspective

“…They play an important role in maintaining the autoimmune tolerance and regulating the duration and amplitude of the physiological immune response to avoid damage and destruction of the normal tissues caused by the immune system. There are few reviews that focus on the area of immune checkpoints 31,32 . Although the immune checkpoint molecules were originally been identified in the T cells, the innate immune cells are becoming a newly emerging target.…”

“…There are few reviews that focus on the area of immune checkpoints. 31 , 32 Although the immune checkpoint molecules were originally been identified in the T cells, the innate immune cells are becoming a newly emerging target. The most classic immune checkpoints are PD‐1 and CTLA‐4 represent the most common immune checkpoints.…”