Gut Microbiota Modulates the Efficiency of Programmed Cell Death Protein 1 Cancer Immunotherapies
Abstract
Program cell death protein 1 (PD1) is considered as an inhibitory molecule that is expressed on the surface of activated T-cells and bound to PD-L1 and PD-L2 ligands. Several types of cancer cells express PD-L1 which can bind to PD1 on the surface of tumor-specific T-cells. PD1/PD-L1 ligation triggers a pathway to protect tumor cells from an effective response of tumor-specific T-cells. Different PD1/PD-L1 blocker antibodies are clinically used to promote the T-cell response against the cancer cells. Current studies suggest that the gut microbiome impacts the efficiency of PD1 blockade therapy in cancer patients. The association of several bacterial species with PD1 responder patients has been determined. The present study reviewed previous reports on the relation between the microbiome and immune checkpoint therapy (ICT). The results of studies were discussed considering adjuvant and molecular mimicry of microbial antigens by tumor-associated antigens and metabolic effects of microbial products on ICT.
1. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat RevImmunol. 2016;16(6):341-8.
2. Gionchetti P, Rizzello F, Helwig U, Venturi A, Lammers KM, Brigidi P, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003;124(5):1202-9.
3. Sutherland L, Singleton J, Sessions J, Hanauer S, Krawitt E, Rankin G, et al. Double blind, placebo controlled trial of metronidazole in Crohn's disease. Gut. 1991;32(9):1071-5.
4. Safari Z, Gérard P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci. 2019;76(8):1541-58.
5. Dehner C, Fine R, Kriegel MA. The microbiome in systemic autoimmune disease: mechanistic insights from recent studies. Curr Opin Rheumatol. 2019;31(2):201-7.
6. Vallianou NG, Stratigou T, Tsagarakis S. Microbiome and diabetes: Where are we now? Diabetes Res Clin Prac. 2018;146:111-8
7. Tseng C-H, Wu C-Y. The gut microbiome in obesity. J Formos Med Assoc. 2019;118:S3-S9.
8. Boursi B, Mamtani R, Haynes K, Yang Y-X. Recurrent antibiotic exposure may promote cancer formation–another step in understanding the role of the human microbiota?. Eur J Cancer. 2015;51(17):2655-64.
9. Zitvogel L, Ayyoub M, Routy B, Kroemer G. Microbiome and anticancer immunosurveillance. Cell. 2016;165(2):276-87.
10. Daillère R, Vétizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016;45(4):931-43.
11. Khedri M, Rafatpanah H, Abnous K, Ramezani P, Ramezani M. Cancer immunotherapy via nucleic acid aptamers. Int immunopharmacol. 2015;29(2):926-36.
12. Capece D, Verzella D, Fischietti M, Zazzeroni F, Alesse E. Targeting costimulatory molecules to improve antitumor immunity. BioMed Res Int. 2012;2012.
13. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology E-book. 8th ed. Elsevier Health Sciences. 2014.
14. Khedri M, Abnous K, Rafatpanah H, Ramezani M. An optimized protocol for the in vitro generation and functional analysis of human PD1/PD-L1 signal. J Recep Sig Transduct. 2018;38(1):31-6.
15. Hamanishi J, Mandai M, Matsumura N, Abiko K, Baba T, Konishi I. PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. Int J Clin Oncol. 2016;21(3):462-73.
16. Inman BA, Longo TA, Ramalingam S, Harrison MR. Atezolizumab: A PD-L1–Blocking Antibody for Bladder Cancer. Clin Cancer Res. 2017;23(8):1886-90.
17. Wang Y, Ma R, Liu F, Lee SA, Zhang L. Modulation of gut microbiota: a novel paradigm of enhancing the efficacy of programmed death-1 and programmed death ligand-1 blockade therapy. Front Immunol. 2018;9:374.
18. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 2015;350(6264):1084-9.
19. Frankel AE, Coughlin LA, Kim J, Froehlich TW, Xie Y, Frenkel EP, et al. Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia. 2017;19(10):848-55.
20. Routy B, Le Chatelier E, Derosa L, Duong CP, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2018;359(6371):91-7.
21. Gopalakrishnan V, Spencer C, Nezi L, Reuben A, Andrews M, Karpinets T, et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103.
22. Xu X, Lv J, Guo F, Li J, Jia Y, Jiang D, et al. Gut microbiome influences the efficacy of PD-1 antibody immunotherapy on MSS-type colorectal cancer via metabolic pathway. Front Microb. 2020;11:814.
23. Zheng Y, Wang T, Tu X, Huang Y, Zhang H, Tan D, et al. Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma. J Immunother Cancer. 2019;7(1):1-7.
24. Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079-84.
25. Christen U, von Herrath MG. Infections and autoimmunity—good or bad? J Immunol. 2005;174(12):7481-6.
26. Fujinami RS, von Herrath MG, Christen U, Whitton JL. Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev. 2006;19(1):80-94.
27. Ménard O, Butel M-J, Gaboriau-Routhiau V, Waligora-Dupriet A-J. Gnotobiotic mouse immune response induced by Bifidobacterium sp. strains isolated from infants. Appl Environ Microbiol. 2008;74(3):660-6.
28. Kawahara T, Takahashi T, Oishi K, Tanaka H, Masuda M, Takahashi S, et al. Consecutive oral administration of Bifidobacterium longum MM‐2 improves the defense system against influenza virus infection by enhancing natural killer cell activity in a murine model. Microbiol and immunol. 2015;59(1):1-12.
29. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369(9573):1627-40.
30. Uribe-Herranz M, Bittinger K, Rafail S, Guedan S, Pierini S, Tanes C, et al. Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12. JCI Insight. 2018;3(4).
31. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N EnglJ Med. 2014;371(23):2189-99.
32. Martin FPJ, Dumas ME, Wang Y, Legido‐Quigley C, Yap IK, Tang H, et al. A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model. Mol Syst Biol. 2007;3(1):112.
33. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-y M, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569-73.
34. VUČENIK I, Stains J. Cancer preventive and therapeutic properties of IP6: efficacy and mechanisms. Period Biologorum. 2010;112(4):451-8.
35. Le Bourgeois T, Strauss L, Aksoylar H-I, Daneshmandi S, Seth P, Patsoukis N, et al. Targeting T cell metabolism for improvement of cancer immunotherapy. Front Oncology. 2018;8:237
36. MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31(5):259-83.
37. Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun. 2015;6:6692.
38. Chang C-H, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell. 2015;162(6):1229-41.
39. Tao R, De Zoeten EF, Özkaynak E, Chen C, Wang L, Porrett PM, et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med. 2007;13(11):1299.
40. Santoni M, Piva F, Conti A, Santoni A, Cimadamore A, Scarpelli M, et al. Re: Gut Microbiome Influences Efficacy of PD-1-based Immunotherapy Against Epithelial Tumors. Eur Urol. 2018;74(4):521.
41. Park J, Kim M, Kang SG, Jannasch AH, Cooper B, Patterson J, et al. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR–S6K pathway. Mucosal Immunol. 2015;8(1):80.
42. Lastwika KJ, Wilson W, Li QK, Norris J, Xu H, Ghazarian SR, et al. Control of PD-L1 expression by oncogenic activation of the AKT–mTOR pathway in non–small cell lung cancer. Cancer Res. 2016;76(2):227-38.
43. Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20(2):145.
44. Erny D, de Angelis ALH, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965.
45. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci. 2011;108(38):16050-5.
46. Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K, et al. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Phyiol Gastrointest Liver Physiol. 2012;303(11):G1288-G95.
47. Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, et al. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe. 2014;16(4):495-503.
2. Gionchetti P, Rizzello F, Helwig U, Venturi A, Lammers KM, Brigidi P, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003;124(5):1202-9.
3. Sutherland L, Singleton J, Sessions J, Hanauer S, Krawitt E, Rankin G, et al. Double blind, placebo controlled trial of metronidazole in Crohn's disease. Gut. 1991;32(9):1071-5.
4. Safari Z, Gérard P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci. 2019;76(8):1541-58.
5. Dehner C, Fine R, Kriegel MA. The microbiome in systemic autoimmune disease: mechanistic insights from recent studies. Curr Opin Rheumatol. 2019;31(2):201-7.
6. Vallianou NG, Stratigou T, Tsagarakis S. Microbiome and diabetes: Where are we now? Diabetes Res Clin Prac. 2018;146:111-8
7. Tseng C-H, Wu C-Y. The gut microbiome in obesity. J Formos Med Assoc. 2019;118:S3-S9.
8. Boursi B, Mamtani R, Haynes K, Yang Y-X. Recurrent antibiotic exposure may promote cancer formation–another step in understanding the role of the human microbiota?. Eur J Cancer. 2015;51(17):2655-64.
9. Zitvogel L, Ayyoub M, Routy B, Kroemer G. Microbiome and anticancer immunosurveillance. Cell. 2016;165(2):276-87.
10. Daillère R, Vétizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016;45(4):931-43.
11. Khedri M, Rafatpanah H, Abnous K, Ramezani P, Ramezani M. Cancer immunotherapy via nucleic acid aptamers. Int immunopharmacol. 2015;29(2):926-36.
12. Capece D, Verzella D, Fischietti M, Zazzeroni F, Alesse E. Targeting costimulatory molecules to improve antitumor immunity. BioMed Res Int. 2012;2012.
13. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology E-book. 8th ed. Elsevier Health Sciences. 2014.
14. Khedri M, Abnous K, Rafatpanah H, Ramezani M. An optimized protocol for the in vitro generation and functional analysis of human PD1/PD-L1 signal. J Recep Sig Transduct. 2018;38(1):31-6.
15. Hamanishi J, Mandai M, Matsumura N, Abiko K, Baba T, Konishi I. PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. Int J Clin Oncol. 2016;21(3):462-73.
16. Inman BA, Longo TA, Ramalingam S, Harrison MR. Atezolizumab: A PD-L1–Blocking Antibody for Bladder Cancer. Clin Cancer Res. 2017;23(8):1886-90.
17. Wang Y, Ma R, Liu F, Lee SA, Zhang L. Modulation of gut microbiota: a novel paradigm of enhancing the efficacy of programmed death-1 and programmed death ligand-1 blockade therapy. Front Immunol. 2018;9:374.
18. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 2015;350(6264):1084-9.
19. Frankel AE, Coughlin LA, Kim J, Froehlich TW, Xie Y, Frenkel EP, et al. Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia. 2017;19(10):848-55.
20. Routy B, Le Chatelier E, Derosa L, Duong CP, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2018;359(6371):91-7.
21. Gopalakrishnan V, Spencer C, Nezi L, Reuben A, Andrews M, Karpinets T, et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103.
22. Xu X, Lv J, Guo F, Li J, Jia Y, Jiang D, et al. Gut microbiome influences the efficacy of PD-1 antibody immunotherapy on MSS-type colorectal cancer via metabolic pathway. Front Microb. 2020;11:814.
23. Zheng Y, Wang T, Tu X, Huang Y, Zhang H, Tan D, et al. Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma. J Immunother Cancer. 2019;7(1):1-7.
24. Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079-84.
25. Christen U, von Herrath MG. Infections and autoimmunity—good or bad? J Immunol. 2005;174(12):7481-6.
26. Fujinami RS, von Herrath MG, Christen U, Whitton JL. Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev. 2006;19(1):80-94.
27. Ménard O, Butel M-J, Gaboriau-Routhiau V, Waligora-Dupriet A-J. Gnotobiotic mouse immune response induced by Bifidobacterium sp. strains isolated from infants. Appl Environ Microbiol. 2008;74(3):660-6.
28. Kawahara T, Takahashi T, Oishi K, Tanaka H, Masuda M, Takahashi S, et al. Consecutive oral administration of Bifidobacterium longum MM‐2 improves the defense system against influenza virus infection by enhancing natural killer cell activity in a murine model. Microbiol and immunol. 2015;59(1):1-12.
29. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369(9573):1627-40.
30. Uribe-Herranz M, Bittinger K, Rafail S, Guedan S, Pierini S, Tanes C, et al. Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12. JCI Insight. 2018;3(4).
31. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N EnglJ Med. 2014;371(23):2189-99.
32. Martin FPJ, Dumas ME, Wang Y, Legido‐Quigley C, Yap IK, Tang H, et al. A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model. Mol Syst Biol. 2007;3(1):112.
33. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-y M, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569-73.
34. VUČENIK I, Stains J. Cancer preventive and therapeutic properties of IP6: efficacy and mechanisms. Period Biologorum. 2010;112(4):451-8.
35. Le Bourgeois T, Strauss L, Aksoylar H-I, Daneshmandi S, Seth P, Patsoukis N, et al. Targeting T cell metabolism for improvement of cancer immunotherapy. Front Oncology. 2018;8:237
36. MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31(5):259-83.
37. Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun. 2015;6:6692.
38. Chang C-H, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell. 2015;162(6):1229-41.
39. Tao R, De Zoeten EF, Özkaynak E, Chen C, Wang L, Porrett PM, et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med. 2007;13(11):1299.
40. Santoni M, Piva F, Conti A, Santoni A, Cimadamore A, Scarpelli M, et al. Re: Gut Microbiome Influences Efficacy of PD-1-based Immunotherapy Against Epithelial Tumors. Eur Urol. 2018;74(4):521.
41. Park J, Kim M, Kang SG, Jannasch AH, Cooper B, Patterson J, et al. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR–S6K pathway. Mucosal Immunol. 2015;8(1):80.
42. Lastwika KJ, Wilson W, Li QK, Norris J, Xu H, Ghazarian SR, et al. Control of PD-L1 expression by oncogenic activation of the AKT–mTOR pathway in non–small cell lung cancer. Cancer Res. 2016;76(2):227-38.
43. Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20(2):145.
44. Erny D, de Angelis ALH, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965.
45. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci. 2011;108(38):16050-5.
46. Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K, et al. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Phyiol Gastrointest Liver Physiol. 2012;303(11):G1288-G95.
47. Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, et al. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe. 2014;16(4):495-503.
| Files | ||
| Issue | Vol 21 No 1 (2022) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i1.8607 | |
| Keywords | ||
| Gastrointestinal microbiome Immunotherapy Neoplasms Programmed cell death 1 receptor | ||
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How to Cite
1.
Samei A, Khedri M. Gut Microbiota Modulates the Efficiency of Programmed Cell Death Protein 1 Cancer Immunotherapies. Iran J Allergy Asthma Immunol. 2022;21(1):1-11.
