Pingyangmycin enhances the antitumor efficacy of anti-PD-1 therapy associated with tumor-infiltrating CD8
Animals
Antibodies
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Bleomycin
/ administration & dosage
CD8-Positive T-Lymphocytes
/ immunology
Cell Line, Tumor
Female
Lymphocytes, Tumor-Infiltrating
/ metabolism
Mammary Neoplasms, Animal
/ drug therapy
Melanoma, Experimental
/ drug therapy
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Tumor Microenvironment
/ immunology
Anti-PD-1
Breast cancer
CD8+ tumor infiltrating lymphocytes
Pingyangmycin
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
26
08
2020
accepted:
20
11
2020
pubmed:
4
1
2021
medline:
24
6
2021
entrez:
3
1
2021
Statut:
ppublish
Résumé
To investigate the antitumor efficacy of pingyangmycin (PYM) in combination with anti-PD-1 antibody and determine the capability of PYM to induce immunogenic cell death (ICD) in cancer cells. The murine 4T1 breast cancer and B16 melanoma models were used for evaluation of therapeutic efficacy of the combination of PYM with anti-PD-1 antibody. The ELISA kits were used to quantify the ICD related ATP and HMGB1 levels. The Transwell assay was conducted to determine the chemotaxis ability of THP-1 cell in vitro. The flow cytometry was used to measure reactive oxygen species level and analyze the ratio of immune cell subsets. PYM induced ICD in murine 4T1 breast cancer and B16 melanoma cells and increased the release of nucleic acid fragments that may further promote the monocytic chemotaxis. In the 4T1 murine breast cancer model, PYM alone, anti-PD-1 antibody alone, and their combination suppressed tumor growth by 66.3%, 16.1% and 77.6%, respectively. PYM markedly enhanced the therapeutic efficacy of anti-PD-1 antibody against 4T1 breast cancer. The calculated CDI (coefficient of drug interaction) indicated synergistic effect. Evaluated by graphic analysis, the nucleated cells intensity in the femur bone marrow remained unchanged. Histopathological observations revealed no noticeable toxico-pathological changes in the lung and various organs, indicating that the PYM and anti-PD-1 antibody combination exerted enhanced efficacy at well-tolerated dosage level. By the combination treatment, a panel of immunological changes emerged. The ratio of CD3 The studies indicate that PYM, as an ICD inducer with mild myelosuppression effect, may enhance the therapeutic efficacy of anti-PD-1 antibody in association with tumor infiltrating CD8
Identifiants
pubmed: 33388950
doi: 10.1007/s00280-020-04209-7
pii: 10.1007/s00280-020-04209-7
doi:
Substances chimiques
Antibodies
0
Pdcd1 protein, mouse
0
Programmed Cell Death 1 Receptor
0
Bleomycin
11056-06-7
bleomycetin
5DY91Y7601
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
425-436Références
Luo Q, Zhang L, Luo C, Jiang M (2019) Emerging strategies in cancer therapy combining chemotherapy with immunotherapy. Cancer Lett 454:191–203. https://doi.org/10.1016/j.canlet.2019.04.017
doi: 10.1016/j.canlet.2019.04.017
pubmed: 30998963
Robert C, Schachter J, Long GV et al (2015) Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532. https://doi.org/10.1056/NEJMoa1503093
doi: 10.1056/NEJMoa1503093
pubmed: 25891173
Ansell SM (2019) Pembrolizumab: living up to expectations. Blood 134:1114–1115. https://doi.org/10.1182/blood.2019002417
doi: 10.1182/blood.2019002417
pubmed: 31582369
Mason R, Dearden HC, Nguyen B et al (2020) Combined ipilimumab and nivolumab first-line and after BRAF-targeted therapy in advanced melanoma. Pigment Cell Melanoma Res 33:358–365. https://doi.org/10.1111/pcmr.12831
doi: 10.1111/pcmr.12831
pubmed: 31587511
Smyth EC, Lordick F (2019) Nivolumab for previously treated squamous oesophageal carcinoma. Lancet Oncol 20:1468–1469. https://doi.org/10.1016/S1470-2045(19)30621-7
doi: 10.1016/S1470-2045(19)30621-7
pubmed: 31582356
Genova C, Boccardo S, Mora M et al (2019) Correlation between B7–H4 and survival of non-small-cell lung cancer patients treated with nivolumab. J Clin Med 8:1566. https://doi.org/10.3390/jcm8101566
doi: 10.3390/jcm8101566
pmcid: 6832616
Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72. https://doi.org/10.1146/annurev-immunol-032712-100008
doi: 10.1146/annurev-immunol-032712-100008
pubmed: 23157435
Inoue H, Tani K (2014) Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments. Cell Death Differ 21:39–49. https://doi.org/10.1038/cdd.2013.84
doi: 10.1038/cdd.2013.84
pubmed: 23832118
Golchin S, Alimohammadi R, Rostami Nejad M, Jalali SA (2019) Synergistic antitumor effect of anti-PD-L1 combined with oxaliplatin on a mouse tumor model. J Cell Physiol. https://doi.org/10.1002/jcp.28585
doi: 10.1002/jcp.28585
pubmed: 30941773
Wu J, Waxman DJ (2018) Immunogenic chemotherapy: Dose and schedule dependence and combination with immunotherapy. Cancer Lett 419:210–221. https://doi.org/10.1016/j.canlet.2018.01.050
doi: 10.1016/j.canlet.2018.01.050
pubmed: 29414305
pmcid: 5818299
Gong J, Liu X, Li Y, Zhen Y (2012) Pingyangmycin downregulates the expression of EGFR and enhances the effects of cetuximab on esophageal cancer cells and the xenograft in athymic mice. Cancer Chemother Pharmacol 69:1323–1332. https://doi.org/10.1007/s00280-012-1827-9
doi: 10.1007/s00280-012-1827-9
pubmed: 22311160
Tai K-W, Chang Y-C, Shin-Shen Chou L, Chou M-Y (1998) Cytotoxic effect of pingyangmycin on cultured KB cells. Oral Oncol 34:219–223. https://doi.org/10.1016/S1368-8375(97)00089-4
doi: 10.1016/S1368-8375(97)00089-4
pubmed: 9692057
Sergeyev DS, Godovikova TS, Zarytova VF (1991) Direct cleavage of a DNA fragment by a bleomycin-oligonucleotide derivative. FEBS Lett 280:271–273. https://doi.org/10.1016/0014-5793(91)80309-q
doi: 10.1016/0014-5793(91)80309-q
pubmed: 1707372
Zhang H, Ma Y, Zhang S, et al (2015) Involvement of Ras GTPase-activating protein SH3 domain-binding protein 1 in the epithelial-to-mesenchymal transition-induced metastasis of breast cancer cells via the Smad signaling pathway. Oncotarget https://doi.org/10.18632/oncotarget.3636
Pulaski BA, Ostrand-Rosenberg S (1998) Reduction of established spontaneous mammary carcinoma metastases following immunotherapy with major histocompatibility complex class II and B7.1 cell-based tumor vaccines. Cancer Res 58:1486–1493
pubmed: 9537252
Elliott MR, Chekeni FB, Trampont PC et al (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461:282–286. https://doi.org/10.1038/nature08296
doi: 10.1038/nature08296
pubmed: 19741708
pmcid: 2851546
Cao SS, Zhen YS (1989) Potentiation of antimetabolite antitumor activity in vivo by dipyridamole and amphotericin B. Cancer Chemother Pharmacol 24:181–186. https://doi.org/10.1007/bf00300240
doi: 10.1007/bf00300240
pubmed: 2736709
Chen DS, Mellman I (2013) Oncology meets immunology: the cancer-immunity cycle. Immunity 39:1–10. https://doi.org/10.1016/j.immuni.2013.07.012
doi: 10.1016/j.immuni.2013.07.012
pubmed: 23890059
Mellman I, Coukos G, Dranoff G (2011) Cancer immunotherapy comes of age. Nature 480:480–489. https://doi.org/10.1038/nature10673
doi: 10.1038/nature10673
pubmed: 22193102
pmcid: 3967235
Sathyanarayanan V, Neelapu SS (2015) Cancer immunotherapy: Strategies for personalization and combinatorial approaches. Molec Oncol 9:2043–2053. https://doi.org/10.1016/j.molonc.2015.10.009
doi: 10.1016/j.molonc.2015.10.009
Gotwals P, Cameron S, Cipolletta D et al (2017) Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer 17:286–301. https://doi.org/10.1038/nrc.2017.17
doi: 10.1038/nrc.2017.17
pubmed: 28338065
Buchbinder EI, Desai A (2016) CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition. Am J Clin Oncol 39:98–106. https://doi.org/10.1097/COC.0000000000000239
doi: 10.1097/COC.0000000000000239
pubmed: 26558876
pmcid: 4892769
Vera Aguilera J, Paludo J, McWilliams RR, et al (2020) Chemo-immunotherapy combination after PD-1 inhibitor failure improves clinical outcomes in metastatic melanoma patients. Melanoma Res Publish Ahead of Print https://doi.org/10.1097/CMR.0000000000000669
Zhou J, Wang G, Chen Y et al (2019) Immunogenic cell death in cancer therapy: Present and emerging inducers. J Cell Mol Med 23:4854–4865. https://doi.org/10.1111/jcmm.14356
doi: 10.1111/jcmm.14356
pubmed: 31210425
pmcid: 6653385
Lamberti MJ, Nigro A, Mentucci FM et al (2020) Dendritic cells and immunogenic cancer cell death: a combination for improving antitumor immunity. Pharmaceutics 12:256. https://doi.org/10.3390/pharmaceutics12030256
doi: 10.3390/pharmaceutics12030256
pmcid: 7151083
Zitvogel L, Kepp O, Kroemer G (2011) Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol 8:151–160. https://doi.org/10.1038/nrclinonc.2010.223
doi: 10.1038/nrclinonc.2010.223
pubmed: 21364688
Michaud M, Martins I, Sukkurwala AQ et al (2011) Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 334:1573–1577. https://doi.org/10.1126/science.1208347
doi: 10.1126/science.1208347
pubmed: 22174255
Park J, Kim CG, Shim J-K et al (2018) Effect of combined anti-PD-1 and temozolomide therapy in glioblastoma. Oncoimmunology. https://doi.org/10.1080/2162402X.2018.1525243
doi: 10.1080/2162402X.2018.1525243
pubmed: 30729066
pmcid: 6351089
Li Y, Zhang H, Li Q et al (2020) CDK12/13 inhibition induces immunogenic cell death and enhances anti-PD-1 anticancer activity in breast cancer. Cancer Lett 495:12–21. https://doi.org/10.1016/j.canlet.2020.09.011
doi: 10.1016/j.canlet.2020.09.011
pubmed: 32941949
Lotsberg ML, Wnuk-Lipinska K, Terry S et al (2020) AXL targeting abrogates autophagic flux and induces immunogenic cell death in drug-resistant cancer cells. J Thoracic Oncol 15:973–999. https://doi.org/10.1016/j.jtho.2020.01.015
doi: 10.1016/j.jtho.2020.01.015
Lau TS, Chan LKY, Man GCW et al (2020) Paclitaxel induces immunogenic cell death in ovarian cancer via TLR4/IKK2/SNARE-dependent exocytosis. Cancer Immunol Res 8:1099–1111. https://doi.org/10.1158/2326-6066.CIR-19-0616
doi: 10.1158/2326-6066.CIR-19-0616
pubmed: 32354736
Du B, Waxman DJ (2020) Medium dose intermittent cyclophosphamide induces immunogenic cell death and cancer cell autonomous type I interferon production in glioma models. Cancer Lett 470:170–180. https://doi.org/10.1016/j.canlet.2019.11.025
doi: 10.1016/j.canlet.2019.11.025
pubmed: 31765733
Duraiswamy J, Freeman GJ, Coukos G (2014) Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors–response. Cancer Res 74:633–634. https://doi.org/10.1158/0008-5472.CAN-13-2752
doi: 10.1158/0008-5472.CAN-13-2752
pubmed: 24408920
Woo S-R, Turnis ME, Goldberg MV et al (2012) Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 72:917–927. https://doi.org/10.1158/0008-5472.CAN-11-1620
doi: 10.1158/0008-5472.CAN-11-1620
Krantz D, Hartana CA, Winerdal ME et al (2018) Neoadjuvant chemotherapy reinforces antitumour T cell response in urothelial urinary bladder cancer. Eur Urol 74:688–692. https://doi.org/10.1016/j.eururo.2018.06.048
doi: 10.1016/j.eururo.2018.06.048
pubmed: 30025882
Xiang Y, Chen L, Li L, Huang Y (2020) Restoration and enhancement of immunogenic cell death of cisplatin by coadministration with digoxin and conjugation to HPMA copolymer. ACS Appl Mater Interfaces 12:1606–1616. https://doi.org/10.1021/acsami.9b19323
doi: 10.1021/acsami.9b19323
pubmed: 31804065
Park S-J, Ye W, Xiao R et al (2019) Cisplatin and oxaliplatin induce similar immunogenic changes in preclinical models of head and neck cancer. Oral Oncol 95:127–135. https://doi.org/10.1016/j.oraloncology.2019.06.016
doi: 10.1016/j.oraloncology.2019.06.016
pubmed: 31345380
pmcid: 6662630
Vignali DAA, Collison LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8:523–532. https://doi.org/10.1038/nri2343
doi: 10.1038/nri2343
pubmed: 18566595
pmcid: 2665249
Lee JC, Mehdizadeh S, Smith J et al (2020) Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis. Sci Immunol 5:eaba0759. https://doi.org/10.1126/sciimmunol.aba0759
doi: 10.1126/sciimmunol.aba0759
pubmed: 33008914
Chen G, Emens LA (2013) Chemoimmunotherapy: reengineering tumor immunity. Cancer Immunol Immunother 62:203–216. https://doi.org/10.1007/s00262-012-1388-0
doi: 10.1007/s00262-012-1388-0
pubmed: 23389507
pmcid: 3608094
Banissi C, Ghiringhelli F, Chen L, Carpentier AF (2009) Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model. Cancer Immunol Immunother 58:1627–1634. https://doi.org/10.1007/s00262-009-0671-1
doi: 10.1007/s00262-009-0671-1
pubmed: 19221744
Sistigu A, Viaud S, Chaput N et al (2011) Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. Semin Immunopathol 33:369–383. https://doi.org/10.1007/s00281-011-0245-0
doi: 10.1007/s00281-011-0245-0
pubmed: 21611872