Medizinische Universität Graz - Research portal
Selected Publication:
Zgubic, J.
PRÄDIKTIV UND PROGNOSTISCHE RELEVANZ VON PD-L1 UND TIGIT EXPRESSION IN NICHT-KLEINZELLIGEN LUNGENKARZINOM PATIENTEN/INNEN BEHANDELT MIT IMMUNOTHERAPIE
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2022. pp. 106
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- Authors Med Uni Graz:
- Advisor:
- Brcic Luka
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- Abstract:
- Background Despite progress is made, non-small cell lung carcinoma (NSCLC) remains one of the most deleterious cancerous diseases worldwide. Immune checkpoint inhibitors targeting molecules like PD-1 and PD-L1 are without doubt beneficial for NSCLC patients. Nonetheless, 5-year-survival-rates vary across NSCLC patients eligible to targeted therapy (15% - 50%). Additionally, this therapy can cause “immune-related Adverse Events”, which harbor detrimental potential. Hence, new immunotherapeutic agents are desperately needed. In this regard, TIGIT (T cell immunoglobulin and ITIM domain) might a be promising surface protein; however, clinicopathological data are still scarce. Aim Aim of this study was to analyze the correlation between the expression level of PD-L1 (22c3 and SP263 PD-L1 assays) and TIGIT in first-line pembrolizumab-treated NSCLC-patients. Furthermore, we aimed to analyze the association between the expression levels of the latter three IHC-assays and clinicopathological parameters, including treatment response to pembrolizumab, and overall survival. Methods / Material 36 NSCLC cases treated with pembrolizumab as first-line therapy (PD-L1 TPS ≥50%), with enough tissue for analysis and follow-up data were selected. A panel of three different immunohistochemical markers ((PD-L1 (22C3 and SP263) and TIGIT (BRL047F)) was applied. For PD-L1, the TPS, and for TIGIT, positive immune cells/mm² were assessed. Correlations between PD-L1 and TIGIT expression levels with treatment responses were determined via the Kruskal-Wallis test. The relationship between expression patterns and OS were analyzed by the Kaplan-Meier method. The log-rank test was used for statistical significance testing. Results We found that TIGIT positively correlates to the 22C3 PD-L1 clone (p=0.044, r=0.324) but not with the SP263 clone (p = 0.091). Although we did not observe significant correlation between TIGIT/PD-L1-overexpression and treatment response to pembrolizumab, we did observe that high TIGIT expression (≥100 positive immune cells/mm2) had a tendency towards better OS. Treatment response to pembrolizumab and OS have not been associated with TPS in PD-L1 assays (TPS 50%-100%). Conclusion Despite all limitations of our study, we were able to confirm the concordance between both PD-L1 clones. We also observed slightly higher sensitivity for SP263 compared to 22c3. We could not show that higher PD-L1 scores (TPS 50%-100%) positively correlate with treatment response. We were able to demonstrate positive correlation between TIGIT and 22c3 (p = 0.044, r=0.324) but not with SP263 (p = 0.091). In conclusion, further studies in much bigger cohorts, ideally on resection material, are necessary to analyze the PD-L1/TIGIT-relation more precisely.