2013P - Investigating the clinical relevance of immune checkpoint expression in the peripheral blood of patients with small cell lung cancer (SCLC)

Background

Cytotoxic T lymphocyte antigen 4 (CTLA4) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) immune checkpoints are expressed on tumor-infiltrated immune cells (TILs) in SCLC and represent promising immunotherapy targets. We aimed to assess the frequency and clinical relevance of CTLA4 and TIGIT expression in the peripheral blood (PB) of patients with SCLC.

Methods

PB was obtained from 90 SCLC patients prior to first-line treatment (chemotherapy=61; combination of chemotherapy/anti-PD-L1 inhibitors: n=29). Peripheral blood mononuclear cell (PBMC) cytospins were stained for CTLA4/TIGIT/dapi. CTLA4 and TIGIT protein expression was individually assessed on 1000 intact PBMCs via fluorescence microscopy; the mean % value was used to define high expression of each marker.

Results

CTLA4 and TIGIT were expressed on PBMCs in 95.6% and 100% of patients, respectively, with a mean percentage of positive PBMCs per patient: 27.8% and 34.5%, respectively. Their expression was not associated with clinicopathological parameters or survival outcomes in the entire patient population. However, separate analysis of the chemoimmunotherapy group (n=29 extensive-stage SCLC patients) revealed that high versus low expression of CTLA4 and/or TIGIT was a marker for increased progression-free survival and overall survival (median PFS: 8.7 vs 4.7 months, p=0.000; median OS: 13.9 vs 5.9 months, p=0.038; respectively by Kaplan Meier analysis); on the contrary, no correlation was shown for patients treated with chemotherapy only (median PFS: 6.2 vs 7.9 months, p=0.877 and median OS: 11.6 vs 15.1, p=0.142). Moreover, among extensive-stage patients with high expression of CTLA4 and/or TIGIT on PBMCs (n=45 patients), the administration of chemoimmunotherapy was associated with improved survival rates as compared to those receiving chemotherapy only (median OS: 14 vs 7.8 months, p=0.005).

Conclusions

CTLA4 and TIGIT are frequently expressed on PBMCs of SCLC patients and are correlated with significant clinical benefit from the addition of anti-PD-L1 inhibitors to first-line chemotherapy. Their role as immunotherapy biomarkers in SCLC merits further investigation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.