Treatments with  PD-checkpoint inhibitors are potentially related to adverse events in patients with metastatic Non-Small-Cell-Lung Cancer (mNSCLC).

The article, “PD-1/PD-L1 immuno-checkpoint blockade induces immune-effector cells modulation in metastatic Non-Small-Cell-Lung Cancer (mNSCLC)  patients: a single cell Flow Cytometry approach,” has been recently accepted for publication by Frontiers in Oncology.

It describes the results of a multicenter retrospective immunobiological analysis involving researchers from multiple scientific institutions, including the Sbarro Institute for Cancer Research and Molecular Medicine in Philadelphia, under the direction of Antonio Giordano, M.D., Ph.D., President and founder of the Sbarro Health Research Organization (SHRO). Collaborators include scientists working at the Grand Metropolitan Hospital “Bianchi Melacrino Morelli” in Reggio Calabria, and the universities of Catanzaro, Palermo, Naples, and Siena, Italy.

The study coordinated by Giordano, and led by Pierpaolo Correale, M.D., Ph.D., Ciro Botta, M.D., Ph.D., and Luciano Mutti, M.D., used an innovative bioinformatic analysis to evaluate if PD-1/PD-L1 blocking could trigger autoimmunity.

“Our analysis,” says Giordano, “revealed a clear-cut treatment-related decline in the immunosuppressant cells coupled with an increase of immune cells active against cancer. On the other hand, in the same patients, as a result of the deregulation of specific immune subpopulations (e.g. NKT cells) treatment-related autoantibodies (AAb) rise and multiple immune-related adverse events occur.”

“This study,” continues Correale, “has been designed because there is an urgent need  to achieve a better  characterization of the immune-biological process underlying  the effects of PD-1/PD-L1 immune-checkpoint.”

“This proof-of-concept study shows AAbs’ as well as the immune- monitoring of specific peripheral lymphocyte subsets should be investigated as potential biomarkers of autoimmunity and (potentially) treatment response in patients with NSCLC receiving PD-1/PDL1 immune-checkpoint blockade.”

Mutti concludes: “In order to identify other  possible mechanistic scenarios, there is need of other studies in this direction, including inflammatory and angiogenesis studies but the trail is  blazed.”