Abstract 1080P
Background
Cancer cells affect the normal myelopoiesis favoring the generation of myeloid cells with immunosuppressive and inflammation-associated functions such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Recently, we demonstrated that the antiapoptotic molecule cellular FLICE-inhibitory protein (c-FLIP) that functions as an important modulator of caspase-8 is crucial for the development of monocytic (M)-MDSCs. We speculated that immune checkpoint inhibitor (ICI)-based therapy could affect the FLIP-expressing myeloid cells frequency and functions in non-progressor (NP) non-small cell lung cancer (NSCLC) patients.
Methods
We collected blood samples at two time-points: before ICI treatment (T0) and during the first clinical evaluation (T1). Circulating immune landscape was defined by multiparametric flow cytometry and systemic cytokine levels were tested by multiplex ELISA assay. Peripheral blood mononuclear cells (PBMCs) and CD14+ cells were cryopreserved to evaluate c-FLIP expression and suppressive properties of monocytes, respectively.
Results
We enrolled 35 NSCLC patients treated with ICIs in different lines. According to RECIST criteria and clinical evaluation, patients were classified as responders (13) or non-responders (19). We demonstrated that NP patients at T1 showed an increased frequency of specific subsets of T cells and a contraction of monocytes. Moreover, a reduction of IL-6 level was detected in NP patients after ICIs treatment. Interestingly, we identified a contraction of c-FLIP-expressing M-MDSCs in NP patients at T1 even if NP and progressor (P) patients had the same frequency of this circulating myeloid cell subset at T0. In agreement with c-FLIP expression data, monocytes isolated from both P and NP patients displayed similar immunosuppressive function at T0 but this pro-tumor activity was negatively influenced by c-FLIP-expressing cells contraction at T1 in NP patient cohort.
Conclusions
Overall, our data suggest that ICIs treatment in NSCLC patients may restrain systemic immunosuppression by negatively affecting the frequency of c-FLIP expressing M-MDSCs. C. Frusteri, A. Adamo, S. Pilotto and L. Belluomimi share the first co-authorship; M. Milella, V. Bronte and S. Ugel share the last co-authorship.
Clinical trial identification
Editorial acknowledgement
No editorial assistance in the writing of the abstract.
However, I underline that Cristina Frusteri, Annalisa Adamo, Sara Pilotto, and I share the first co-authorship, and Michele Milella, Vincenzo Bronte, and Stefano Ugel share the last co-authorship.
Legal entity responsible for the study
The authors.
Funding
This work was supported by the PRIN programs of the Italian Ministry of Education, University and Research (MIUR, CUP: B38D19000140006 [U.S.], CUP: CUP B38D19000260006 [V.B.]), Cariverona Fondation (Project call, 2017 [V.B.]), by the Cancer Research Institute (Clinic and Laboratory Integration Program, CLIP-2020[V.B.]) and Fondazione Associazione Italiana per la Ricerca sul Cancro (AIRC, Project: 23788 [V.B.] and 21509 [U.S.]).
Disclosure
All authors have declared no conflicts of interest.