Abstract 166P
Background
CTC detection is a marker of metastatic dissemination in SCLC. Tumor spread has been linked to impaired anti-tumor immune surveillance. The expression of immune checkpoints, such as TIGIT and CTLA4, on tumor-infiltrated immune cells (TILs) holds promising prognostic and therapeutic implications in SCLC, however their role in the peripheral blood (PB) is largely unexplored. We herein assessed CTC detection coupled with CTLA4 and TIGIT expression on peripheral blood mononuclear cells (PBMCs) of SCLC patients.
Methods
PB was obtained from 63 SCLC patients prior to first-line treatment, and PBMC cytospins were prepared. Two distinct immunofluorescence stainings were performed for the detection of CTCs (cytokeratins/CD45) and the immune phenotyping of PBMCs (TIGIT/CTLA4), and samples were analyzed via fluorescence microscopy.
Results
CTCs were identified in 27/63 (42.9%) patients. CTLA4 and TIGIT were frequently expressed on PBMCs (median percentage per patient: 24.8% and 31%, respectively). An increased percentage of CTLA4+ PBMCs and TIGIT+ PBMCs was demonstrated in CTC-positive as compared to CTC-negative patients (Mean Rank: 38.9% versus 26.8%, p = 0.009, and 41.6% vs 24.8%, p = 0.000, respectively, Mann-Whitney U test). A positive correlation was confirmed between the number of CTCs, and the proportion of CTLA4+ PBMCs (p = 0.005) and TIGIT+ PBMCs (p = 0.000). Increased levels of CTLA4+ PBMCs (above median) were more frequently observed in patients with metastatic dissemination to multiple organs (>3 vs 1–2 systems affected: 61.8% vs 36.7%, p = 0.045, Fisher's exact test). The prognostic value of these findings is currently being investigated and will be presented.
Conclusions
CTLA4 and TIGIT expression on PBMCs is frequently observed in SCLC patients and is associated with CTC detection. The analysis of the peripheral blood holds a promising role for the understanding of the metastatic process and immune-surveillance mechanisms in SCLC. The study was partially funded by HESMO (Hellenic Society of Medical Oncology) and ARSA (Anticancer Research Support Association), Heraklion, Greece.
Legal entity responsible for the study
The authors.
Funding
HESMO (Hellenic Society of Medical Oncology) and ARSA (Anticancer Research Support Association), Heraklion, Greece.
Disclosure
All authors have declared no conflicts of interest.