Pirfenidone facilitates immune infiltration and enhances the antitumor efficacy of PD-L1 blockade in mice

References

• Lederer DJ. Martinez FJ: idiopathic pulmonary fibrosis. N Engl J Med. 2018;378:1811–11. doi:10.1056/NEJMra1705751.
   PubMed Web of Science ®Google Scholar
• Zielinski M, Sitek P. Ziora D: idiopathic pulmonary fibrosis coexisting with lung cancer - a review. Adv Respir Med. 2018;86(6):319–326. doi: 10.5603/ARM.a2018.0052.
   Google Scholar
• Tzouvelekis A, Gomatou G, Bouros E, Trigidou R, Tzilas V, Bouros D. Common pathogenic mechanisms between idiopathic pulmonary fibrosis and lung cancer. Chest. 2019. doi:10.1016/j.chest.2019.04.114.
   Google Scholar
• Sato T, Watanabe A, Kondo H, Kanzaiki M, Okubo K, Yokoi K, Marutsuka T, Shinohara H, Teramukai S, Kishi K, et al. Long-term results and predictors of survival after surgical resection of patients with lung cancer and interstitial lung diseases. J Thorac Cardiovasc Surg. 2015;149(64–69):70 e61–62. doi:10.1016/j.jtcvs.2014.08.086.
   Google Scholar
• Chen H, Senan S, Nossent EJ, Boldt RG, Warner A, Palma DA, Louie AV. Treatment-related toxicity in patients with early-stage non-small cell lung cancer and coexisting interstitial lung disease: a systematic review. Int J Radiat Oncol Biol Phys. 2017;98(3):622–631. doi:10.1016/j.ijrobp.2017.03.010.
   PubMed Web of Science ®Google Scholar
• Kudoh S, Kato H, Nishiwaki Y, Fukuoka M, Nakata K, Ichinose Y, Tsuboi M, Yokota S, Nakagawa K, Suga M, et al. Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Am J Respir Crit Care Med. 2008;177(12):1348–1357. doi:10.1164/rccm.200710-1501OC.
   PubMed Web of Science ®Google Scholar
• Raghu G, Rochwerg B, Zhang Y, Garcia CAC, Azuma A, Behr J, Brozek JL, Collard HR, Cunningham W, Homma S, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3–19. doi:10.1164/rccm.201506-1063ST.
   PubMed Web of Science ®Google Scholar
• Qin W, Liu B, Yi M, Li L, Tang Y, Wu B, Yuan X. Antifibrotic agent pirfenidone protects against development of radiation-induced pulmonary fibrosis in a murine model. Radiat Res. 2018;190(4):396–403. doi:10.1667/RR15017.1.
   PubMed Web of Science ®Google Scholar
• Selvaggio AS. Noble PW: pirfenidone initiates a new era in the treatment of idiopathic pulmonary fibrosis. Annu Rev Med. 2016;67:487–495. doi:10.1146/annurev-med-120214-013614.
   PubMed Web of Science ®Google Scholar
• Kwapiszewska G, Gungl A, Wilhelm J, Marsh LM, Thekkekara Puthenparampil H, Sinn K, Didiasova M, Klepetko W, Kosanovic D, Schermuly RT, et al. Transcriptome profiling reveals the complexity of pirfenidone effects in IPF. Eur Respir J. 2018;1800564. doi:10.1183/13993003.00564-2018
   PubMed Web of Science ®Google Scholar
• Aboulkheyr Es H, Zhand S, Thiery JP, Warkiani ME. Pirfenidone reduces immune-suppressive capacity of cancer-associated fibroblasts through targeting CCL17 and TNF-beta. Integr Biol (Camb). 2020;12(7):188–197. doi:10.1093/intbio/zyaa014.
   PubMed Web of Science ®Google Scholar
• Marwitz S, Turkowski K, Nitschkowski D, Weigert A, Brandenburg J, Reiling N, Thomas M, Reck M, Dromann D, Seeger W, et al. The multi-modal effect of the anti-fibrotic drug pirfenidone on NSCLC. Front Oncol. 2019;9:1550.doi: 10.3389/fonc.2019.01550.
   Web of Science ®Google Scholar
• Gubens MA. Davies M: NCCN guidelines updates: new immunotherapy strategies for improving outcomes in non-small cell lung cancer. J Natl Compr Canc Netw. 2019;17:574–578.
   PubMed Web of Science ®Google Scholar
• Gajewski TF. The next hurdle in cancer immunotherapy: overcoming the non-T-cell-inflamed tumor microenvironment. Semin Oncol. 2015;42:663–671. doi:10.1053/j.seminoncol.2015.05.011.
   PubMed Web of Science ®Google Scholar
• Tauriello DVF, Palomo-Ponce S, Stork D, Berenguer-Llergo A, Badia-Ramentol J, Iglesias M, Sevillano M, Ibiza S, Cañellas A, Hernando-Momblona X, et al. TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis. Nature. 2018;554:538–543. doi:10.1038/nature25492.
   PubMed Web of Science ®Google Scholar
• Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y, Kadel III EE, Koeppen H, Astarita JL, Cubas R, et al. TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554(7693):544–548. doi:10.1038/nature25501.
   PubMed Web of Science ®Google Scholar
• Holmgaard RB, Schaer DA, Li Y, Castaneda SP, Murphy MY, Xu X, Inigo I, Dobkin J, Manro JR, Iversen PW, et al. Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade. J Immuno Ther Cancer. 2018;6(1). doi:10.1186/s40425-018-0356-4.
   PubMedGoogle Scholar
• Lan Y, Zhang D, Xu C, Hance KW, Marelli B, Qi J, Yu H, Qin G, Sircar A, Hernández VM, et al. Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-beta. Sci Transl Med. 2018;10. doi:10.1126/scitranslmed.aan5488
   PubMed Web of Science ®Google Scholar
• Yi M, Liu B, Tang Y, Li F, Qin W, Yuan Xianglin. Irradiated human umbilical vein endothelial cells undergo endothelial-mesenchymal transition via the snail/miR-199a-5p axis to promote the differentiation of fibroblasts into myofibroblasts. Biomed Res Int. 2018;4135806:2018
   Google Scholar
• Du J, Paz K, Flynn R, Vulic A, Robinson TM, Lineburg KE, Alexander KA, Meng J, Roy S, Panoskaltsis-Mortari A, et al. Pirfenidone ameliorates murine chronic GVHD through inhibition of macrophage infiltration and TGF-beta production. Blood. 2017;129:2570–2580. doi:10.1182/blood-2017-01-758854.
   PubMed Web of Science ®Google Scholar
• Ochi H, Abraham M, Ishikawa H, Frenkel D, Yang K, Basso AS, Wu H, Chen M-L, Gandhi R, Miller A, et al. Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25- LAP+ T cells. Nat Med. 2006;12:627–635. doi:10.1038/nm1408.
   PubMed Web of Science ®Google Scholar
• Gandhi R, Anderson DE. Weiner HL: cutting edge: immature human dendritic cells express latency-associated peptide and inhibit T cell activation in a TGF-beta-dependent manner. J Immunol. 2007;178:4017–4021. doi:10.4049/jimmunol.178.7.4017.
   PubMedGoogle Scholar
• Lin H, Wei S, Hurt EM, Green MD, Zhao L, Vatan L, Szeliga W, Herbst R, Harms PW, Fecher LA, et al. Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression. J Clin Invest. 2018;128:1708. doi:10.1172/JCI120803.
   PubMed Web of Science ®Google Scholar
• Juneja VR, McGuire KA, Manguso RT, LaFleur MW, Collins N, Haining WN, Freeman GJ, Sharpe AH. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J Exp Med. 2017;214(4):895–904. doi:10.1084/jem.20160801.
   PubMed Web of Science ®Google Scholar
• Mosely SI, Prime JE, Sainson RC, Koopmann J-O, Wang DYQ, Greenawalt DM, Ahdesmaki MJ, Leyland R, Mullins S, Pacelli L, et al. Rational selection of syngeneic preclinical tumor models for immunotherapeutic drug discovery. Cancer Immunol Res. 2017;5(1):29–41. doi:10.1158/2326-6066.CIR-16-0114.
   PubMed Web of Science ®Google Scholar
• D’Alterio C, Buoncervello M, Ierano C, Napolitano M, Portella L, Rea G, Barbieri A, Luciano A, Scognamiglio G, Tatangelo F, et al. Targeting CXCR4 potentiates anti-PD-1 efficacy modifying the tumor microenvironment and inhibiting neoplastic PD-1. J Exp Clin Cancer Res. 2019;38:432.
   Web of Science ®Google Scholar
• Nagarsheth N, Wicha MS. Zou W: chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol. 2017;17:559–572.
   PubMed Web of Science ®Google Scholar
• Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, King TE, Lancaster L, Sahn SA, Szwarcberg J, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377(9779):1760–1769. doi:10.1016/S0140-6736(11)60405-4.
   PubMed Web of Science ®Google Scholar
• King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083–2092.
   PubMed Web of Science ®Google Scholar
• Miura Y, Saito T, Tanaka T, Takoi H, Yatagai Y, Inomata M, Nei T, Saito Y, Gemma A, Azuma A, et al. Reduced incidence of lung cancer in patients with idiopathic pulmonary fibrosis treated with pirfenidone. Respir Investig. 2018;56(1):72–79. doi:10.1016/j.resinv.2017.09.007.
   PubMed Web of Science ®Google Scholar
• Kanayama M, Mori M, Matsumiya H, Taira A, Shinohara S, Kuwata T, Imanishi N, Yoneda K, Kuroda K, Tanaka F, et al. Perioperative pirfenidone treatment for lung cancer patients with idiopathic pulmonary fibrosis. Surg Today. 2020;50:469–474. doi:10.1007/s00595-019-01923-5.
   PubMed Web of Science ®Google Scholar
• Fujiwara A, Shintani Y, Funaki S, Kawamura T, Kimura T, Minami M, Okumura M. Pirfenidone plays a biphasic role in inhibition of epithelial-mesenchymal transition in non-small cell lung cancer. Lung Cancer. 2017;106:8–16. doi:10.1016/j.lungcan.2017.01.006.
   PubMed Web of Science ®Google Scholar
• Kozono S, Ohuchida K, Eguchi D, Ikenaga N, Fujiwara K, Cui L, Mizumoto K, Tanaka M. Pirfenidone inhibits pancreatic cancer desmoplasia by regulating stellate cells. Cancer Res. 2013;73:2345–2356.
   PubMed Web of Science ®Google Scholar
• Ishii K, Sasaki T, Iguchi K, Kato M, Kanda H, Hirokawa Y, Arima K, Watanabe M, Sugimura Y. Pirfenidone, an anti-fibrotic drug, suppresses the growth of human prostate cancer cells by inducing g1 cell cycle arrest. J Clin Med. 2019;8(1):44. doi:10.3390/jcm8010044.
   PubMed Web of Science ®Google Scholar
• Zou WJ, Huang Z, Jiang TP, Shen Y-P, Zhao A-S, Zhou S, Zhang S. Pirfenidone inhibits proliferation and promotes apoptosis of hepatocellular carcinoma cells by inhibiting the wnt/beta-catenin signaling pathway. Med Sci Monit. 2017;23:6107–6113. doi:10.12659/MSM.907891.
   PubMed Web of Science ®Google Scholar
• Kramer M, Markart P, Drakopanagiotakis F, Mamazhakypov A, Schaefer L, Didiasova M, Wygrecka M. Pirfenidone inhibits motility of NSCLC cells by interfering with the urokinase system. Cell Signal. 2020;65:109432. doi:10.1016/j.cellsig.2019.109432.
   PubMed Web of Science ®Google Scholar
• Li C, Rezov V, Joensuu E, Vartiainen V, Rönty M, Yin M, Myllärniemi M, Koli K. Pirfenidone decreases mesothelioma cell proliferation and migration via inhibition of ERK and AKT and regulates mesothelioma tumor microenvironment in vivo. Sci Rep. 2018;8(1):10070. doi:10.1038/s41598-018-28297-x.
   PubMedGoogle Scholar
• Mediavilla-Varela M, Boateng K, Noyes D, Antonia SJ. The anti-fibrotic agent pirfenidone synergizes with cisplatin in killing tumor cells and cancer-associated fibroblasts. BMC Cancer. 2016;16(1):176. doi:10.1186/s12885-016-2162-z.
   PubMedGoogle Scholar
• Akhurst RJ. Targeting TGF-beta signaling for therapeutic gain. Cold Spring Harb Perspect Biol. 2017;9(10):a022301. doi:10.1101/cshperspect.a022301.
   PubMed Web of Science ®Google Scholar
• Dadrich M, Nicolay NH, Flechsig P, Bickelhaupt S, Hoeltgen L, Roeder F, Hauser K, Tietz A, Jenne J, Lopez R, et al. Combined inhibition of TGFβ and PDGF signaling attenuates radiation-induced pulmonary fibrosis. Oncoimmunology. 2016;5(5):e1123366. doi:10.1080/2162402X.2015.1123366.
   PubMed Web of Science ®Google Scholar
• Yingling JM, McMillen WT, Yan L, Huang H, Sawyer JS, Graff J, Clawson DK, Britt KS, Anderson BD, Beight DW, et al. Preclinical assessment of galunisertib (LY2157299 monohydrate), a first-in-class transforming growth factor-beta receptor type I inhibitor. Oncotarget. 2018;9:6659–6677. doi:10.18632/oncotarget.23795.
   PubMedGoogle Scholar
• Reagan‐Shaw S, Nihal M, Ahmad N. Ahmad N: dose translation from animal to human studies revisited. Faseb J. 2008;22(3):659–661. doi:10.1096/fj.07-9574LSF.
   PubMed Web of Science ®Google Scholar