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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.

Publication ,  Journal Article
Huang, L; Qiao, G; Morse, MA; Wang, X; Zhou, X; Wu, J; Hobeika, A; Ren, J; Lyerly, HK
Published in: Oncol Lett
December 2019

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.

Duke Scholars

Published In

Oncol Lett

DOI

ISSN

1792-1074

Publication Date

December 2019

Volume

18

Issue

6

Start / End Page

5717 / 5724

Location

Greece

Related Subject Headings

  • 3211 Oncology and carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Huang, L., Qiao, G., Morse, M. A., Wang, X., Zhou, X., Wu, J., … Lyerly, H. K. (2019). 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. Oncol Lett, 18(6), 5717–5724. https://doi.org/10.3892/ol.2019.10964
Huang, Lefu, Guoliang Qiao, Michael A. Morse, Xiaoli Wang, Xinna Zhou, Jiangping Wu, Amy Hobeika, Jun Ren, and Herbert K. Lyerly. “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.Oncol Lett 18, no. 6 (December 2019): 5717–24. https://doi.org/10.3892/ol.2019.10964.
Huang, Lefu, et al. “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.Oncol Lett, vol. 18, no. 6, Dec. 2019, pp. 5717–24. Pubmed, doi:10.3892/ol.2019.10964.
Huang L, Qiao G, Morse MA, Wang X, Zhou X, Wu J, Hobeika A, Ren J, Lyerly HK. 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. Oncol Lett. 2019 Dec;18(6):5717–5724.

Published In

Oncol Lett

DOI

ISSN

1792-1074

Publication Date

December 2019

Volume

18

Issue

6

Start / End Page

5717 / 5724

Location

Greece

Related Subject Headings

  • 3211 Oncology and carcinogenesis