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Oxaliplatin facilitates tumor-infiltration of T cells and natural-killer cells for enhanced tumor immunotherapy in lung cancer model
Platinum is reported to have adjuvant immune properties, whether oxaliplatin (OXA) could be utilized to synergize with anti-programmed cell death-1 (PD-1) antibody or anti-NKG2D (natural-killer group 2, member D) antibody is investigated. Subcutaneous A549 lung cancer and murine Lewis lung carcinoma...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8734624/ https://www.ncbi.nlm.nih.gov/pubmed/34561996 http://dx.doi.org/10.1097/CAD.0000000000001248 |
Sumario: | Platinum is reported to have adjuvant immune properties, whether oxaliplatin (OXA) could be utilized to synergize with anti-programmed cell death-1 (PD-1) antibody or anti-NKG2D (natural-killer group 2, member D) antibody is investigated. Subcutaneous A549 lung cancer and murine Lewis lung carcinoma (LLC) models were constructed, which were further intravenously injected with platinum-based drugs or concomitant administrated with anti-PD-1 antibody and or anti-NKG2D antibody. The tumor volume and the proportion of myeloid cells (CD45(+)CD11b(+)), CD3(+)T cells and NK (NK1.1(+)) cells were detected. The relative expression of chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10 and CXCL11 and C-X-C motif chemokine receptor 3 (CXCR3) was detected with the ELISA, western blot and flow cytometry. The three platinum drugs (cisplatin, DDP; carboplatin, CBP; OXA) showed similar effects to inhibit A549 tumor growth in immune-deficient mice. While OXA exhibited better antitumor efficacy in wild-type mice bearing LLC with downregulated myeloid cells proportion, upregulated concentration of CXCL9, CXCL10 and CXCL11, and upregulated proportion and CXCR3 expression on T cells and NK cells. OXA combined with anti-PD1 or anti-NKG2D synergistically improved tumor growth inhibition and survival. The combination of OXA to anti-PD1 and anti-NKG2D antibodies will provide the most appropriate treatment benefit. Oxaliplatin promotes T cells and NK cells infiltration through the CXCL9/10/11-CXCR3 axis to enhance anti-PD1 or anti-NKG2D immunotherapy in lung cancer. |
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