Open Access

Immune checkpoint inhibitors modulate the cytotoxic effect of chemotherapy in lung adenocarcinoma cells

  • Authors:
    • Marika Saar
    • Darja Lavogina
    • Helen Lust
    • Hannes Tamm
    • Jana Jaal
  • View Affiliations

  • Published online on: March 3, 2023     https://doi.org/10.3892/ol.2023.13738
  • Article Number: 152
  • Copyright: © Saar et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Immunotherapy using immune checkpoint inhibitors (ICIs) has significantly improved survival in patients with non‑small cell lung cancer (NSCLC), and ICIs are increasingly used in combination with cytotoxic treatments, such as chemotherapy. Although combined treatments are more effective, not all patients respond to the therapy; therefore, a detailed understanding of the effect of treatment combinations at the tumour level is needed. The present study aimed to explore whether ICIs could affect the cytotoxic effects of chemotherapy on lung adenocarcinoma cell lines with different PD‑L1 expression levels (high, HCC‑44; low, A‑549). Using the resazurin‑based assay, the efficacy of seven chemotherapeutic agents (cisplatin, etoposide, gemcitabine, pemetrexed, vinorelbine, docetaxel and paclitaxel) was compared in the presence or absence of the individually chosen single doses of four ICIs (nivolumab, pembrolizumab, atezolizumab and durvalumab). The results revealed that different ICIs can exhibit either potentiating or depotentiating effects, depending on the chemotherapy agent or lung adenocarcinoma cell line used. Durvalumab was the most promising ICI, which potentiated most chemotherapy agents in both cell lines, especially in the case of high PD‑L1 expression. By contrast, nivolumab, exhibited depotentiating trends in several combinations. The immunostaining of γH2AX in treated cells confirmed that the potentiation of the chemotherapeutic cytotoxicity by durvalumab was at least partially mediated via increased DNA damage; however, this effect was strongly dependent on the chemotherapy agent and cell line used. Our future studies aim to address the specific mechanisms underlying the observed ICI‑induced potentiation or depotentiation.
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April-2023
Volume 25 Issue 4

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Spandidos Publications style
Saar M, Lavogina D, Lust H, Tamm H and Jaal J: Immune checkpoint inhibitors modulate the cytotoxic effect of chemotherapy in lung adenocarcinoma cells. Oncol Lett 25: 152, 2023
APA
Saar, M., Lavogina, D., Lust, H., Tamm, H., & Jaal, J. (2023). Immune checkpoint inhibitors modulate the cytotoxic effect of chemotherapy in lung adenocarcinoma cells. Oncology Letters, 25, 152. https://doi.org/10.3892/ol.2023.13738
MLA
Saar, M., Lavogina, D., Lust, H., Tamm, H., Jaal, J."Immune checkpoint inhibitors modulate the cytotoxic effect of chemotherapy in lung adenocarcinoma cells". Oncology Letters 25.4 (2023): 152.
Chicago
Saar, M., Lavogina, D., Lust, H., Tamm, H., Jaal, J."Immune checkpoint inhibitors modulate the cytotoxic effect of chemotherapy in lung adenocarcinoma cells". Oncology Letters 25, no. 4 (2023): 152. https://doi.org/10.3892/ol.2023.13738