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

Oncoimmunology. 2023 Apr 26;12(1):2204745. doi: 10.1080/2162402X.2023.2204745. eCollection 2023.

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 progressors and 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.

Trial registration: ClinicalTrials.gov NCT04082988 NCT03446911.

Keywords: NSCLC; PD-1 inhibitor; PET–CT; T-cell profiling; TDLN; biomarker; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Non-Small-Cell Lung* / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Fluorodeoxyglucose F18
  • Humans
  • Lung Neoplasms* / diagnostic imaging
  • Lung Neoplasms* / drug therapy
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / pathology
  • Positron Emission Tomography Computed Tomography
  • Positron-Emission Tomography
  • Programmed Cell Death 1 Receptor

Substances

  • Fluorodeoxyglucose F18
  • Programmed Cell Death 1 Receptor

Associated data

  • ClinicalTrials.gov/NCT04082988
  • ClinicalTrials.gov/NCT03446911

Grants and 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.