Reprogrammed CD8+ T-Lymphocytes Isolated from Bone Marrow Have Anticancer Potential in Lung Cancer

Autor: Evgenii G. Skurikhin, Olga Pershina, Natalia Ermakova, Angelina Pakhomova, Darius Widera, Mariia Zhukova, Edgar Pan, Lubov Sandrikina, Lena Kogai, Nikolai Kushlinskii, Sergey G. Morozov, Aslan Kubatiev, Alexander Dygai
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Biomedicines, Vol 10, Iss 6, p 1450 (2022)
Druh dokumentu: article
ISSN: 2227-9059
DOI: 10.3390/biomedicines10061450
Popis: 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.
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