AUTHOR=Bronte Giuseppe , Verlicchi Alberto , De Matteis Serena , Rossi Alice , Affatato Alessandra , Sullo Francesco Giulio , Gianni Caterina , Canale Matteo , Burgio Marco Angelo , Delmonte Angelo , Milella Michele , Crinò Lucio 

TITLE=Case Report: Circulating Myeloid-Derived Suppressive-Like Cells and Exhausted Immune Cells in Non-Small Cell Lung Cancer Patients Treated With Three Immune Checkpoint Inhibitors

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.672219

DOI=10.3389/fimmu.2021.672219

ISSN=1664-3224

ABSTRACT=Immune checkpoint inhibition induced a great step forward in the treatment of non-small cell lung cancer patients. In cancer immune microenvironment many checkpoints were studied and their involvement could represent a mechanism of resistance to cancer immunotherapy. For this reason the inhibition of multiple immune checkpoints is under development. However, myeloid-derived suppressor cells (MDSC) and exhausted immune cells could limit the efficacy of cancer immunotherapy. We analyzed the variation of circulating immune suppressive cell subsets in three non-small cell lung cancer patients treated with the combination of anti-CTLA-4 plus anti-PD-1 plus anti-LAG-3. We also describe the clinical and radiological course of the disease during this treatment in all three patients. We evaluated blood samples at three time points: T0 (baseline), T1 (after 2 months), T2 (after 4 months). We observed an increased mobilization of polymorphonuclear MDSC (CD15+HLA-DR-/lowCD11b+CD33+) and a reduction of monocytic MDSC (CD14+HLA-DR-/lowCD11b+CD33+) in peripheral blood. We also observed a boost of T, NK and NKT cells co-expressing PD-1 and LAG-3 at T2 during combination immunotherapy. These findings suggest that combination immunotherapy induces variation in the composition of immune suppressive cell subsets. The study on a wider patient population and experimental model design could help to clarify these findings.