Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.

Huang, Lefu

Qiao, Guoliang

Morse, Michael A

Wang, Xiaoli

Zhou, Xinna

Wu, Jiangping

Hobeika, Amy

Ren, Jun

Lyerly, Herbert K

2020-01-08T03:02:08Z

2020-01-08T03:02:08Z

2019-12

2020-01-08T03:02:05Z

Adoptive T cell immunotherapy with cytokine-induced killer cells (CIKs) has been demonstrated to prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate whether the expansion of effector T cells and the decrease of regulatory T cells (Tregs) that occurred during the ex vivo generation of DC-CIKs were associated with improved clinical outcome in patients who received treatment. CIKs were generated ex vivo over a 28-day period from the peripheral blood apheresis product of 163 patients with advanced cancer (including 30 with NSCLC). CIKs were also generated from an additional cohort of 65 patients with NSCLC over a 15-day period. The progression-free survival (PFS) and overall survival (OS) time of patients treated with CIKs was determined by reviewing the patients' medical records. The number of CIKs gradually increased during the culture period and peaked at day 15, followed by a slight decline until day 28. Similarly, the percentages of T cell subtypes associated with anti-tumor activity (CD3+, CD3+CD4+, CD3+CD8+ and CD8+CD28+) peaked at day 15. Although the percentage of CD4+CD25+CD127+ Tregs increased by day 7, a decrease was subsequently observed. Among the 95 patients with NSCLC, those with a post/pre-culture ratio of CD8+CD28+ T lymphocytes >2.2 had significantly better PFS and OS compared with those with ratios ≤2.2. Those with a post/pre-culture CD4+CD25+CD127+ Treg ratio ≤0.6 had significantly better OS and PFS compared with those with ratios >0.6. The peak expansion of CIKs from peripheral blood mononuclear cells occurred at day 15 of ex vivo culture. PFS and OS were associated with post/pre-culture CD8+CD28+ T lymphocyte ratio >2.2 and post/pre-culture CD4+CD25+CD127+ Treg ratio <0.6 in the CIKs of patients with advanced NSCLC treated with adoptive T cell immunotherapy. Further efforts are underway to optimize the DC-CIK infusion for cancer immunotherapy.

OL-0-0-10964

1792-1074

1792-1082

https://hdl.handle.net/10161/19748

eng

Spandidos Publications

Oncology letters

10.3892/ol.2019.10964

T lymphocyte phenotype

advanced non-small cell lung cancer

dendritic cell-cytokine-induced killer cell immunotherapy

ex vivo culture

regulatory T cells

Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.

Journal article

Lyerly, Herbert K|0000-0002-0063-4770

5717

5724

6

School of Medicine

Duke

Duke Cancer Institute

Institutes and Centers

Surgery, Surgical Sciences

Surgery

Clinical Science Departments

Medicine, Medical Oncology

Medicine

Immunology

Basic Science Departments

Duke Global Health Institute

University Institutes and Centers

Institutes and Provost's Academic Units

Pathology

Published

18