Early response evaluation of PD-1 blockade in NSCLC patients through FDG-PET-CT and T cell profiling of tumor-draining lymph nodes

ABSTRACT

Better biomarkers for programmed death - (ligand) 1 (PD-(L)1) checkpoint blockade in non-small cell lung cancer (NSCLC) are needed. We explored the predictive value of early response evaluation using Fluor-18-deoxyglucose positron emission tomography and pre- and on-treatment flowcytometric T-cell profiling in peripheral blood and tumor-draining lymph nodes (TDLN). The on-treatment evaluation was performed 7–14 days after the start of PD-1 blockade in NSCLC patients. These data were related to (pathological) tumor response, progression-free survival, and overall survival (OS). We found that increases in total lesion glycolysis (TLG) had a strong reverse correlation with OS (r = −0.93, p = 0.022). Additionally, responders showed decreased and progressors increased Treg frequencies on-treatment. Frequencies of detectable PD-1-expressing CD8⁺ T cells decreased in responders but remained stable in progressors. This was especially found in the TDLN. Changes in activated Treg rates in TDLN were strongly but, due to low numbers of data points, non-significantly correlated with ΔTLG and reversely correlated with OS.

KEYWORDS:

• NSCLC
• immunotherapy
• biomarker
• PET–CT
• TDLN
• PD-1 inhibitor
• T-cell profiling

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availablity satatement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2204745.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This research was funded by Bristol Myers Squibb (NCT 04082988) and Merck Sharpe & Dohme (NCT 03446911). Both were involved neither in the study design nor in the data collection, analysis and interpretation of data, or the writing of this report.