BMC cancer, 2022-07, Vol.22 (1), p.727-727, Article 727
2022
Details
- Autor(en) / Beteiligte
- Titel
- Improving anticancer effect of aPD-L1 through lowering neutrophil infiltration by PLAG in tumor implanted with MB49 mouse urothelial carcinoma
- Ist Teil von
- BMC cancer, 2022-07, Vol.22 (1), p.727-727, Article 727
- Ort / Verlag
- England: BioMed Central Ltd
- Erscheinungsjahr
- 2022
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- The PD-L1 antibody is an immune checkpoint inhibitor (ICI) attracting attention. The third-generation anticancer drug has been proven to be very effective due to fewer side effects and higher tumor-specific reactions than conventional anticancer drugs. However, as tumors produce additional resistance in the host immune system, the effectiveness of ICI is gradually weakening. Therefore, it is very important to develop a combination therapy that increases the anticancer effect of ICI by removing anticancer resistance factors present around the tumor. The syngeneic model was used (n = 6) to investigate the enhanced anti-tumor effect of PD-L1 antibody with the addition of PLAG. MB49 murine urothelial cancer cells were implanted into the C57BL/6 mice subcutaneously. PLAG at different dosages (50/100 mpk) was daily administered orally for another 4 weeks with or without 5 mpk PD-L1 antibody (10F.9G2). PD-L1 antibody was delivered via IP injection once a week. The aPD-L1 monotherapy group inhibited tumor growth of 56% compared to the positive group, while the PLAG and aPD-L1 co-treatment inhibited by 89%. PLAG treatment effectively reduced neutrophils infiltrating localized in tumor and converted to a tumor microenvironment with anti-tumor effective T-cells. PLAG increased tumor infiltration of CD8 positive cytotoxic T-cell populations while effectively inhibiting the infiltration of neoplastic T-cells such as CD4/FoxP3. Eventually, neutrophil-induced tumor ICI resistance was resolved by restoring the neutrophil-to-lymphocyte ratio to the normal range. In addition, regulation of cytokine and chemokine factors that inhibit neutrophil infiltration and increase the killing activity of cytotoxic T cells was observed in the tumors of mice treated with PLAG + aPD-L1. PLAG effectively turned the tumor-promoting microenvironment into a tumor-suppressing microenvironment. As a molecule that increases the anti-tumor effectiveness of aPD-L1, PLAG has the potential to be an essential and effective ICI co-therapeutic agent.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1471-2407eISSN: 1471-2407DOI: 10.1186/s12885-022-09815-7Titel-ID: cdi_doaj_primary_oai_doaj_org_article_b867c1e8f1ce434ca17d91a07270e1d7
- Format
- –
- Schlagworte
- Analysis, Animals, Anti-PD-L1, Antibodies, Antineoplastic drugs, Antitumor agents, B7-H1 Antigen, Bladder cancer, Cancer, Carcinoma, Carcinoma, Transitional Cell - drug therapy, Care and treatment, CD4 antigen, CD8 antigen, Chemokines, Cytokines, Cytotoxicity, Development and progression, Drug therapy, Evaluation, Foxp3 protein, Immune checkpoint inhibitors, Immune system, Immunosuppressive agents, Infiltration, Leukocytes (neutrophilic), Lymphocytes, Lymphocytes T, Manufacturers, Metastases, Mice, Mice, Inbred C57BL, Neutrophil Infiltration, Neutrophil-to-lymphocyte ratio, Neutrophils, Oral administration, PD-L1 protein, PLAG, T cells, Tumor Microenvironment, Tumor-infiltrating lymphocytes, Tumors, Urinary Bladder Neoplasms - drug therapy, Urothelial cancer, Urothelial carcinoma, Viral antibodies