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Commentary

The interplay between cholesterol (and other metabolic conditions) and immune-checkpoint immunotherapy: shifting the concept from the “inflamed tumor” to the “inflamed patient”

ORCID Icon, ORCID Icon & ORCID Icon
Pages 1930-1934 | Received 30 Sep 2020, Accepted 12 Nov 2020, Published online: 10 Jan 2021

References

  • Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009;2(5–6):231–37. doi:10.1242/dmm.001180.
  • Yang H-Y, Wu C-Y, Powell JD, Lu K-L. Manipulation of metabolic pathways and its consequences for anti-tumor immunity: a clinical perspective. Int J Mol Sci. 2020 Jun 4;21(11):4030. doi:10.3390/ijms21114030.
  • Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, Mandruzzato S, Murray PJ, Ochoa A, Ostrand-Rosenberg S. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016;7(1):12150. doi:10.1038/ncomms12150.
  • Safari E, Ghorghanlu S, Ahmadi-Khiavi H, Mehranfar S, Rezaei R, Motallebnezhad M. Myeloid-derived suppressor cells and tumor: current knowledge and future perspectives. J Cell Physiol. 2019;234(7):9966–81. doi:10.1002/jcp.27923.
  • Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015 Apr;14(4):847–56. doi:10.1158/1535-7163.MCT-14-0983.
  • Porta C, Marino A, Consonni FM, Bleve A, Mola S, Storto M, Riboldi E, Sica A. Metabolic influence on the differentiation of suppressive myeloid cells in cancer. Carcinogenesis. 2018;39(9):1095–104. doi:10.1093/carcin/bgy088.
  • Sica A, Strauss L. Energy metabolism drives myeloid-derived suppressor cell differentiation and functions in pathology. J Leukoc Biol. 2017;102(2):325–34. doi:10.1189/jlb.4MR1116-476R.
  • Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44. doi:10.1038/nature07205.
  • Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480–89. doi:10.1038/nature10673.
  • Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45. doi:10.1016/S0140-6736(00)04046-0.
  • Perrone F, Minari R, Bersanelli M, Bordi P, Tiseo M, Favari E, Sabato R, Buti S. The prognostic role of high blood cholesterol in advanced cancer patients treated with immune checkpoint inhibitors. J Immunother. 2020 Jul/Aug;43(6):196–203. doi:10.1097/CJI.0000000000000321.
  • Gautier EL, Huby T, Saint-Charles F, Ouzilleau B, Pirault J, Deswaerte V, Ginhoux F, Miller ER, Witztum JL, Chapman MJ. Conventional dendritic cells at the crossroads between immunity and cholesterol homeostasis in atherosclerosis. Circulation. 2009 May 5;119(17):2367–75. doi:10.1161/CIRCULATIONAHA.108.807537.
  • Bersanelli M, Leonetti A, Buti S. The link between calcitriol and anticancer immunotherapy: vitamin D as the possible balance between inflammation and autoimmunity in the immune-checkpoint blockade. Immunotherapy. 2017 Nov;9(14):1127–31.
  • Poels K, van Leent MMT, Reiche ME, Kusters PJH, Huveneers S, de Winther MPJ, Mulder WJM, Lutgens E, Seijkens TTP. Antibody-mediated inhibition of CTLA4 aggravates atherosclerotic plaque inflammation and progression in hyperlipidemic mice. Cells. 2020 Aug 29;9(9):E1987. doi:10.3390/cells9091987.
  • Yang W, Bai Y, Xiong Y, Zhang J, Chen S, Zheng X, Meng X, Li L, Wang J, Xu C. Potentiating the antitumor response of CD8+ T cells by modulating cholesterol metabolism. Nature. 2016;531(7596):651–55. doi:10.1038/nature17412.
  • Fan Z, Liu H, Xue Y, Lin J, Fu Y, Xia Z, Pan D, Zhang J, Qiao K, Zhang Z, et al. Reversing cold tumors to hot: an immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy. Bioact Mater. 2020 Aug 28;6(2):312–25. doi:10.1016/j.bioactmat.2020.08.005.
  • Janji B, Hasmim M, Parpal S, De Milito A, Berchem G, Noman MZ. Lighting up the fire in cold tumors to improve cancer immunotherapy by blocking the activity of the autophagy-related protein PIK3C3/VPS34. Autophagy. 2020 Sep;5:1–2.
  • Bersanelli M, Buti S. From targeting the tumor to targeting the immune system: transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis. World J Clin Oncol. 2017 Feb 10;8(1):37–53. doi:10.5306/wjco.v8.i1.37.
  • Sanmamed MF, Chen L, Paradigm A. Shift in cancer immunotherapy: from enhancement to normalization. Cell. 2019 Jan 24;176(3):677. doi:10.1016/j.cell.2019.01.008.
  • Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM. Prolonged survival in stage iii melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016 Nov 10;375(19):1845–55. doi:10.1056/NEJMoa1611299.
  • Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015 Oct 22;373(17):1627–39. doi:10.1056/NEJMoa1507643.
  • Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015 Jul 9;373(2):123–35. doi:10.1056/NEJMoa1504627.
  • Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277–90. doi:10.1056/NEJMoa1712126.
  • Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017 Oct 5;377(14):1345–56. doi:10.1056/NEJMoa1709684.
  • Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823–33. doi:10.1056/NEJMoa1606774.
  • Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016 Nov 10;375(19):1856–67. doi:10.1056/NEJMoa1602252.
  • Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803–13.
  • Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulović S, Demey W, Ullén A. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218–30. doi:10.1056/NEJMoa2002788.
  • Giròn-Ulloa A, Gonzàlez-Domìnguez E, Klimek RS, et al. Specific macrophage subsets accumulate in human subcutaneous and omental fat depots during obesity. Immunol Cell Biol. 2020 Jul 22. doi:10.1111/imcb.12380.
  • Pauken KE, Wherry EJ. Overcoming T cell exhaustion in infection and cancer. Trends Immunol. 2015 Apr;36(4):265–76. doi:10.1016/j.it.2015.02.008.
  • Young AC, Quach HT, Song H, Davis EJ, Moslehi JJ, Ye F, Williams GR, Johnson DB. Impact of body composition on outcomes from anti-PD1 ± anti-CTLA-4 treatment in melanoma. J Immunother Cancer. 2020 Jul;8(2):e000821. doi:10.1136/jitc-2020-000821.
  • McQuade JL, Daniel CR, Hess KR, Mak C, Wang DY, Rai RR, Park JJ, Haydu LE, Spencer C, Wongchenko M. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Lancet Oncol. 2018 Mar;19(3):310–22. doi:10.1016/S1470-2045(18)30078-0.
  • Cortellini A, Bersanelli M, Buti S, Cannita K, Santini D, Perrone F, Giusti R, Tiseo M, Michiara M, Di Marino P, et al. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable. J Immunother Cancer. 2019;7(1):57. doi:10.1186/s40425-019-0527-y.
  • Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. Body fatness and cancer—viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794–98. doi:10.1056/NEJMsr1606602.
  • Choi Y, Park B, Jeong BC, Seo SI, Jeon SS, Choi HY, Adami H-O, Lee JE, Lee HM. Body mass index and survival in patients with renal cell carcinoma: a clinical-based cohort and meta-analysis. Int J Cancer. 2013;132(3):625–34. doi:10.1002/ijc.27639.
  • Hakimi AA, Furberg H, Zabor EC, Jacobsen A, Schultz N, Ciriello G, Mikklineni N, Fiegoli B, Kim PH, Voss MH. An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J Natl Cancer Inst. 2013;105(24):1862–70. doi:10.1093/jnci/djt310.
  • Sanchez A, Furberg H, Kuo F, Vuong, L, Ged Y, Patil S, Ostrovnaya I, Petruzella S, Reising A, Patel P, et al. Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: a cohort study. Lancet Oncol. 2019 Dec 20. published online. doi:10.1016/S1470-2045(19)30797-1.
  • Cortellini A, Bersanelli M, Santini D, Buti S, Tiseo M, Cannita K, Perrone F, Giusti R, De Tursi M, Zoratto F, et al. Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: A multicentre analysis of immune-related adverse events. Eur J Cancer. 2020 Mar;128:17–26.
  • Centanni M, Moes DJAR, Troco´niz IF, Ciccolini J, van Hasselt JGC. Clinical pharmacokinetics and pharmacodynamics of immune checkpoint inhibitors. Clin Pharmacokinet. 2019;58(7):835e57. doi:10.1007/s40262-019-00748-2.
  • Sosa A, Lopez Cadena E, Simon Olive C, Karachaliou N, Rosell R. Clinical assessment of immune-related adverse events. Ther Adv Med Oncol. 2018. 10:1758835918764628. doi:10.1177/1758835918764628.
  • Bomze D, Hasan Ali O, Bate A, Flatz L. Association between immune-related adverse events during anti-PD-1 therapy and tumor mutational burden [published online ahead of print, 2019 Aug 22]. JAMA Oncol. 2019;5(11):1633–35. doi:10.1001/jamaoncol.2019.3221.
  • Berner F, Bomze D, Diem S, Ali OH, Fässler M, Ring S, Niederer R, Ackermann CJ, Baumgaertner P, Pikor N. Association of checkpoint inhibitor-induced toxic effects with shared cancer and tissue antigens in non-small cell lung cancer [published correction appears in JAMA Oncol. 2019 Jul 1;5(7):1070]. JAMA Oncol. 2019;5(7):1043–47. doi:10.1001/jamaoncol.2019.0402.
  • Cortellini A, Buti S, Santini D, Perrone F, Giusti R, Tiseo M, Bersanelli M, Michiara M, Grassadonia A, Brocco D. Clinical outcomes of patients with advanced cancer and pre-existing autoimmune diseases treated with anti-programmed death-1 immunotherapy: a real-world transverse study. Oncologist. 2019 Jun;24(6):e327–e337. doi:10.1634/theoncologist.2018-0618.
  • Cortellini A, Buti S, Agostinelli V, Bersanelli M. A systematic review on the emerging association between the occurrence of immune-related adverse events and clinical outcomes with checkpoint inhibitors in advanced cancer patients. Semin Oncol. 2019 Aug-Oct;46(4–5):362–71. Epub 2019 Nov 7. PMID: 31727344. doi:10.1053/j.seminoncol.2019.10.003.
  • Xingzhe M, Enguang B, Yong L, Su P, Huang C, Liu L, Wang Q, Yang M, Kalady MF, Qian J. Cholesterol induces CD8 + T cell exhaustion in the tumor microenvironment. Cell Metab. 2019 Jul 2;30(1):143–156.e5. doi:10.1016/j.cmet.2019.04.002.
  • Elahi S, Weiss RH, Merani S. Atorvastatin restricts HIV replication in CD4+ T cells by upregulation of p21. AIDS. 2016 Jan;30(2):171–83. doi:10.1097/QAD.0000000000000917.

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