Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Evaluation of Antitumor Activity of Reprogrammed Spleen CD8+ T-Cells in a Lewis Lung Cancer Mouse Model

Olga Pershina
* ORCID logo ,
Angelina Pakhomova
ORCID logo ,
Natalia Ermakova
ORCID logo ,
Edgar Pan
ORCID logo ,
Evgenii G. Skurikhin
,
Darius Widera
ORCID logo ,
Lubov Sandrikina
,
Lena Kogai
,
Mariia Zhukova
ORCID logo ,
Vadim Zhdanov
,
Nikolai Kushlinskii
,
Sergey Morozov
,
Aslan Kubatiev
,
Alexander Dygai
Version 1 : Received: 17 April 2024 / Approved: 17 April 2024 / Online: 18 April 2024 (14:22:11 CEST)

How to cite: Pershina, O.; Pakhomova, A.; Ermakova, N.; Pan, E.; Skurikhin, E.G.; Widera, D.; Sandrikina, L.; Kogai, L.; Zhukova, M.; Zhdanov, V.; Kushlinskii, N.; Morozov, S.; Kubatiev, A.; Dygai, A. Evaluation of Antitumor Activity of Reprogrammed Spleen CD8+ T-Cells in a Lewis Lung Cancer Mouse Model. Preprints 2024, 2024041191. https://doi.org/10.20944/preprints202404.1191.v1 Pershina, O.; Pakhomova, A.; Ermakova, N.; Pan, E.; Skurikhin, E.G.; Widera, D.; Sandrikina, L.; Kogai, L.; Zhukova, M.; Zhdanov, V.; Kushlinskii, N.; Morozov, S.; Kubatiev, A.; Dygai, A. Evaluation of Antitumor Activity of Reprogrammed Spleen CD8+ T-Cells in a Lewis Lung Cancer Mouse Model. Preprints 2024, 2024041191. https://doi.org/10.20944/preprints202404.1191.v1

Abstract

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

Keywords

reprogrammed spleen CD8+ T-cells; Lewis lung carcinoma; cancer stem cell; CD8+ and CD4+ T-cells; antimetastatic activity

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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