Reprogrammed CD8+ T-lymphocytes isolated from bone marrow have anticancer potential in lung cancer

Skurikhin, E. G., Pershina, O. ORCID: https://orcid.org/0000-0002-0468-0272, Ermakova, N., Pakhomova, A. ORCID: https://orcid.org/0000-0003-0725-1323, Widera, D. ORCID: https://orcid.org/0000-0003-1686-130X, Zhukova, M. ORCID: https://orcid.org/0000-0002-8146-2279, Pan, E. ORCID: https://orcid.org/0000-0002-2163-7647, Sandrikina, L., Kogai, L., Kushlinskii, N., Morozov, S. G., Kubatiev, A. and Dygai, A. (2022) Reprogrammed CD8+ T-lymphocytes isolated from bone marrow have anticancer potential in lung cancer. Biomedicines, 10 (6). 1450. ISSN 2227-9059 doi: 10.3390/biomedicines10061450

Abstract/Summary

CD8+ T-lymphocytes play a key role in antitumor immune response. Patients with lung cancer often suffer from T-lymphocyte dysfunction and low T-cell counts. The exhaustion of effector T-lymphocytes largely limits the effectiveness of therapy. In this study, reprogrammed T-lymphocytes used MEK inhibitors and PD-1 blockers to increase their antitumor activity. Antitumor effects of reprogrammed T-lymphocytes were shown in vitro and in vivo in the Lewis lung carcinoma model. The population of T- lymphocytes with persistent expression of CCR7 was formed as a result of reprogramming. Reprogrammed T-lymphocytes were resistant to apoptosis and characterized by high cytotoxicity against Lewis lung carcinoma (LLC) cells in vitro. Administration of reprogrammed T-lymphocytes to C57BL/6 mice with LLC reduced the number of lung metastases. The antitumor effect resulted from the elimination of tumor cells and cancer stem cells, and the effect of therapy on cytotoxic T-lymphocyte counts. Thus, reprogramming of T-lymphocytes using MEK inhibitors is a promising approach for targeted therapy of lung cancer.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/106579
Identification Number/DOI	10.3390/biomedicines10061450
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Medicinal Chemistry Research Group
Publisher	MDPI
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