{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yang B"],"funding":["Science and Technology Commission of Shanghai Municipality","Clinical Trial Funding of Shanghai Changzheng Hospital","National Natural Science Foundation of China"],"pagination":["1297-1309"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9747853"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["45(6)"],"pubmed_abstract":["

Purpose

Our study intended to explore how low-dose anti-angiogenic drugs affected anti-tumor immunity of tumor-infiltrating exhausted CD8+T cells and achieved better clinical response when combined with immunotherapy. We set out to find potential targets or predictive biomarker on CD8+T cells for immunotherapy.

Methods

We tested different doses of anti-VEGFR2 antibody combined with anti-PD1 antibody to treat LUAD in vivo and analyzed tumor-infiltrating CD8+T cells by flow cytometry. CD8+T cells overexpressing LAYN were co-cultured with LA795 cell lines to identify the function of LAYN in CD8+T cells. We also analyzed clinical samples from advanced LUAD patients treated with anti-angiogenesis therapy combined with immunotherapy.

Results

Low-dose anti-VEGFR2 antibody combined with anti-PD1 antibody treatment delayed tumor growth and prolonged the survival time of tumor-bearing mice. The number of tumor-infiltrating CD8+T cells was reduced and the expression of LAYN was down-regulated in tumor-infiltrating CD8+T cells in the low-dose anti-VEGFR2 combination group. It was found that LAYN inhibited the killing function of CD8+T cells. In patients with advanced LUAD who received anti-angiogenesis therapy combined with immunotherapy, the LAYN+CD8+T cell subpopulation in good responders was significantly higher than that in poor responders. Furthermore, we demonstrated the expression of LAYN was regulated by upstream transcription factor NR4A1.

Conclusion

Low-dose anti-VEGFR2 antibody combined with anti-PD1 antibody therapy promoted anti-tumor immunity and the downregulation of LAYN in tumor-infiltrating CD8+T cells played an important role in this process. These findings had implications for improving the efficacy of immune checkpoint blockade therapy and further optimized clinical treatment guidelines in advanced LUAD."],"journal":["Cellular oncology (Dordrecht)"],"pubmed_title":["Low-dose anti-VEGFR2 therapy promotes anti-tumor immunity in lung adenocarcinoma by down-regulating the expression of layilin on tumor-infiltrating CD8+T cells."],"pmcid":["PMC9747853"],"funding_grant_id":["81702249, 2017","20Y11914400, 2022","2020YLCYJ-Z03, 2020","82172710, 2021"],"pubmed_authors":["Deng B","Zhang W","Guo Y","Li D","Lu Y","Yang B","Li B","Jiao XD","Chen S","Qin BD","Zang YS"],"additional_accession":[]},"is_claimable":false,"name":"Low-dose anti-VEGFR2 therapy promotes anti-tumor immunity in lung adenocarcinoma by down-regulating the expression of layilin on tumor-infiltrating CD8+T cells.","description":"

Purpose

Our study intended to explore how low-dose anti-angiogenic drugs affected anti-tumor immunity of tumor-infiltrating exhausted CD8+T cells and achieved better clinical response when combined with immunotherapy. We set out to find potential targets or predictive biomarker on CD8+T cells for immunotherapy.

Methods

We tested different doses of anti-VEGFR2 antibody combined with anti-PD1 antibody to treat LUAD in vivo and analyzed tumor-infiltrating CD8+T cells by flow cytometry. CD8+T cells overexpressing LAYN were co-cultured with LA795 cell lines to identify the function of LAYN in CD8+T cells. We also analyzed clinical samples from advanced LUAD patients treated with anti-angiogenesis therapy combined with immunotherapy.

Results

Low-dose anti-VEGFR2 antibody combined with anti-PD1 antibody treatment delayed tumor growth and prolonged the survival time of tumor-bearing mice. The number of tumor-infiltrating CD8+T cells was reduced and the expression of LAYN was down-regulated in tumor-infiltrating CD8+T cells in the low-dose anti-VEGFR2 combination group. It was found that LAYN inhibited the killing function of CD8+T cells. In patients with advanced LUAD who received anti-angiogenesis therapy combined with immunotherapy, the LAYN+CD8+T cell subpopulation in good responders was significantly higher than that in poor responders. Furthermore, we demonstrated the expression of LAYN was regulated by upstream transcription factor NR4A1.

Conclusion

Low-dose anti-VEGFR2 antibody combined with anti-PD1 antibody therapy promoted anti-tumor immunity and the downregulation of LAYN in tumor-infiltrating CD8+T cells played an important role in this process. These findings had implications for improving the efficacy of immune checkpoint blockade therapy and further optimized clinical treatment guidelines in advanced LUAD.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-18T19:20:38.024Z","creation":"2025-04-07T07:01:15.017Z"},"accession":"S-EPMC9747853","cross_references":{"pubmed":["36260222"],"doi":["10.1007/s13402-022-00718-0"]}}