Tumor Immunogenic Cell Death as a Mediator of Intratumor CD8 T-Cell Recruitment

The success of anticancer treatments relies on a long-term response which can be mediated by the immune system. Thus, the concept of immunogenic cell death (ICD) describes the capacity of dying cancer cells, under chemotherapy or physical stress, to express or release danger-associated molecular patterns (DAMPs). These DAMPs are essential to activate dendritic cells (DCs) and to stimulate an antigen presentation to CD8 cytotoxic cells. Then, activated CD8 T cells exert their antitumor effects through cytotoxic molecules, an effect which is transitory due to the establishment of a feedback loop leading to T-cell exhaustion. This phenomenon can be reversed using immune checkpoint blockers (ICBs), such as anti-PD-1, PD-L1 or CTLA-4 Abs. However, the blockade of these checkpoints is efficient only if the CD8 T cells are recruited within the tumor. The CD8 T-cell chemoattraction is mediated by chemokines. Hence, an important question is whether the ICD can not only influence the DC activation and resulting CD8 T-cell activation but can also favor the chemokine production at the tumor site, thus triggering their recruitment. This is the aim of this review, in which we will decipher the role of some chemokines (and their specific receptors), shown to be released during ICD, on the CD8 T-cell recruitment and antitumor response. We will also analyze the clinical applications of these chemokines as predictive or prognostic markers or as new targets which should be used to improve patients' response.

Automated summary

The success of anticancer treatments depends on the ability of dying cancer cells under chemotherapy or physical stress to activate immune cells and stimulate an antitumor response. This can be achieved through the release of danger-associated molecular patterns (DAMPs) and the recruitment of CD8 T cells. However, the effectiveness of immune checkpoint blockers in reversing T-cell exhaustion is dependent on the recruitment of CD8 T cells within the tumor. Chemokines play a crucial role in CD8 T-cell recruitment. This review aims to explore the role of chemokines released during immunogenic cell death (ICD) in CD8 T-cell recruitment and antitumor response, as well as their potential clinical applications.