Summary and future perspectives 245 7 Conclusion This thesis has made several contributions to the field of biomarkers and its diagnostic approaches related to predicting clinical outcomes in advanced-stage NSCLC patients treated with PD-1 blockade therapy. The key findings can be summarized as follows: 1) We have established the presence of a distinct population of tumor-reactive T cells, known as PD-1T TILs, as a novel biomarker for long-term benefit to PD-1 blockade in NSCLC with high NPV. 2) We have observed that selected biomarker combinations did not improve predictive accuracy when compared to PD-1T TILs as a single biomarker. 3) We have developed a robust PD-1T gene signature, reflecting a tumor’s PD-1T TIL status, offering a more practical and readily implementable option for routine clinical diagnostics. 4) A serum-based protein signature has been constructed, allowing for outcome stratification without the need for invasive tissue biopsies. 5) Finally, we have demonstrated the efficacy of cfDNA extracted from the supernatant of pleural effusion for the accurate detection of targetable oncogenes and resistance mechanisms. Together, these findings advance our capacity to tailor treatment strategies and diagnostic approaches for advanced-stage NSCLC patients undergoing PD-1 blockade therapy.
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