Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial

Clin Transl Med. 2021 Jul;11(7):e491. doi: 10.1002/ctm2.491.


Background: Immunotherapy is being tested in early-stage non-small cell lung cancer (NSCLC), and achieving higher rates of complete pathological responses (CPR) as compared to standard of care. Early identification of CPR patients has vital clinical implications. In this study, we focused on basal peripheral immune cells and their treatment-related changes to find biomarkers associated to CPR.

Methods: Blood from 29 stage IIIA NSCLC patients participating in the NADIM trial (NCT03081689) was collected at diagnosis and post neoadjuvant treatment. More than 400 parameters of peripheral blood mononuclear cells (PBMCs) phenotype and plasma soluble factors were analyzed.

Results: Neoadjuvant chemoimmunotherapy altered more than 150 immune parameters. At diagnosis, 11 biomarkers associated to CPR were described, with an area under the ROC curve >0.70 and p-value <.05. CPR patients had significantly higher levels of CD4+ PD-1+ cells, NKG2D, and CD56 expression on T CD56 cells, intensity of CD25 expression on CD4+ CD25hi+ cells and CD69 expression on intermediate monocytes; but lower levels of CD3+ CD56- CTLA-4+ cells, CD14++ CD16+ CTLA-4+ cells, CTLA-4 expression on T CD56 cells and lower levels of b-NGF, NT-3, and VEGF-D in plasma compared to non-CPR. Post treatment, CPR patients had significantly higher levels of CD19 expression on B cells, BCMA, 4-1BB, MCSF, and PARC and lower levels of MPIF-1 and Flt-3L in plasma compared to non-CPR.

Conclusions: Patients achieving CPR seem to have a distinctive peripheral blood immune status at diagnosis, even showing different immune response to treatment. These results reinforce the different biology behind CPR and non-CPR responses.

Keywords: biomarkers; chemoimmunotherapy; immune cells; neoadjuvant; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD19 / metabolism
  • Antineoplastic Agents / therapeutic use
  • Area Under Curve
  • B-Cell Maturation Antigen / blood
  • Biomarkers, Tumor / blood*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Immunotherapy
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Nerve Growth Factor / blood
  • Neurotrophin 3 / blood
  • ROC Curve
  • Vascular Endothelial Growth Factor D / blood


  • Antigens, CD19
  • Antineoplastic Agents
  • B-Cell Maturation Antigen
  • Biomarkers, Tumor
  • Neurotrophin 3
  • Vascular Endothelial Growth Factor D
  • Nerve Growth Factor

Associated data