MerTK Signaling in Human Primary T cells Modulates Memory Potential and Improves Recall response.

Immune therapy using checkpoint inhibitors or adoptive cell transfer has revolutionized the treatment of several types of cancers. However, response to treatment is currently limited to a fraction of patients. Elucidation of immune modulatory mechanisms might optimize patient selection and present ways to modify anti-cancer immune responses.

STAT3 inhibitor Napabucasin abrogates MDSC immunosuppressive capacity and prolongs survival of melanoma-bearing mice.

Background: Myeloid-derived suppressor cells (MDSCs) represent a negative prognostic factor in malignant melanoma. These cells are generated under chronic inflammatory conditions typical of cancer. The transcription factor signal transducer and activator of transcription 3 (STAT3) orchestrates MDSC accumulation and acquisition of immunosuppressive properties.

Tumor promoting capacity of polymorphonuclear myeloid-derived suppressor cells and their neutralization.

Myeloid-derived suppressor cells (MDSC) represent a highly immunosuppressive population that expands in tumor bearing hosts and inhibits both T and NK cell antitumor effector functions. Among MDSC subpopulations, the polymorphonuclear (PMN) one is gaining increasing interest since it is a predominant MDSC subset in most cancer entities and inherits unique properties to facilitate metastatic spread. In addition, further improvement in distinguishing PMN-MDSC from neutrophils has contributed to the design of novel therapeutic approaches.

Thioredoxin activity confers resistance against oxidative stress in tumor-infiltrating NK cells.

To improve the clinical outcome of adoptive NK cell therapy in patients with solid tumors, NK cells need to persist within the tumor microenvironment (TME) in which the abundance of ROS could dampen antitumor immune responses. In the present study, we demonstrated that IL-15-primed NK cells acquired resistance against oxidative stress through the thioredoxin system activated by mTOR. Mechanistically, the activation of thioredoxin showed dependence on localization of thioredoxin-interacting protein.