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C. Frati
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-062 - Impact of the Tissue Distribution of Subpopulations of TILs and PD-L1 Expression on the Clinical Outcome of NSCLC (ID 5715)
14:30 - 14:30 | Author(s): C. Frati
- Abstract
Background:
The number and function of tumor infiltrating lymphocytes (TILs) represent an important prognostic factor in cancer. Among the multiple immune escape mechanisms triggered by cancer, the PD-1/PD-L1 checkpoint seems to play a central role. Accordingly, PD-1/PD-L1 inhibitors have shown significant clinical results in multiresistant NSCLC. However, the role of this immune checkpoint on tumor biology and clinical outcome remains to be determined. To this end, the number and distribution of subpopulations of TILs together with the quantification of PD-L1 expression were immunohistochemically assessed in NSCLC and their impact on patients survival evaluated.
Methods:
Histologic sections from 106 NSCLC (46 ADC,60 SCC) were morphometrically analysed after immunohistochemical assessment of the incidence of CD3+, CD8+ and PD-1+ TILs and their proximal or distal location with respect to neoplastic cells. A comparative evaluation between immuneperoxidase and immunofluorescence (IF) on control tissues and on serial sections from the same cases was undertaken using three different anti-PD-L1 antibodies (clones:28-8,SP142 and M4420). Following suitability criteria, PD-L1 was measured by confocal quantitative IF. Neoplastic and stromal expression of PD-L1 was ascertained by the simultaneous IF detection of Cytokeratin (CK). Morphometric data and clinical records were subjected to Kaplan Meier estimation.
Results:
The gradient of lymphocyte subsets according to their hierarchical phenotype was maintained in both NSCLC, however, the number of CD3[+] TILs was 1.8-fold higher in ADC vs SCC in the presence of similar density of CD8[+] and PD-1[+ ]cells. EGFR and K-RAS mutations conditioned the ADC immune microenvironment by altering CD8[+] and PD-1[+] distribution. High intra- and inter-patients variability in PD-L1 levels was expectedly observed although the average value in SCC samples was higher compared to ADC . K-RAS and to a less extent EGFR mutations were associated with a lower PD-L1 expression. Significant PD-L1 labelling of stromal cells was present in 10% of cases. Interestingly, a lower expression of CK in cells with high PD-L1 signal and the occasional presence of neoplastic plugs overexpressing PD-L1 and lacking CK were documented. Although the number of TILs and PD-L1 levels tended to positively correlate with OS in the entire population of NSCLC, in the individulal cohort of ADC and SCC patients only low number of intratumor PD-1[+] lymphocytes was statistically associated with a significant increased (>10months) OS.
Conclusion:
High levels of PD-L1 and reduction of its cellular target are associated with improved clinical outcome in NSCLC suggesting that adoption by TILs of local escape from PD-L1 pressure delays tumor progression.
