Table Info

Table 1.

Microbial species which may enhance the effect of immune-checkpoint cancer therapies

Immunotherapies	Microbial species	References
Anti PD-1/PD-L1 blockade	Bacteroides cellulosilyticus Bifidobacterium dentium Coprococcus comes Lactobacillus oris Lactobacillus mucosae Streptococcus thermophilus	[69, 74]
Anti CTLA-4 blockade	Bacteroides thetaiotaomicron Bacteroides fragilis Burkholderia cepacia Faecalibacterium genus	[74, 101]

Immunotherapies

Microbial species

References

Anti PD-1/PD-L1 blockade

Bacteroides cellulosilyticus

Bifidobacterium dentium

Coprococcus comes

Lactobacillus oris

Lactobacillus mucosae

Streptococcus thermophilus

[69, 74]

Anti CTLA-4 blockade

Bacteroides thetaiotaomicron

Bacteroides fragilis

Burkholderia cepacia

Faecalibacterium genus

[74, 101]

Declarations

Author contributions

SY and SM: Conceptualization. SY, KT, HS, YI, TA, AT and SM: Writing—original draft, Writing—review & editing. All authors contributed to manuscript revision, read, and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Perisetti A, Goyal H, Yendala R, Chandan S, Tharian B, Thandassery RB. Sarcopenia in hepatocellular carcinoma: current knowledge and future directions. World J Gastroenterol. 2022;28:432–48. [DOI] [PubMed] [PMC]

Canale M, Ulivi P, Foschi FG, Scarpi E, De Matteis S, Donati G, et al. Clinical and circulating biomarkers of survival and recurrence after radiofrequency ablation in patients with hepatocellular carcinoma. Crit Rev Oncol Hematol. 2018;129:44–53. [DOI] [PubMed]

Choi JW, Lee JM, Lee DH, Yoon JH, Kim YJ, Lee JH, et al. Radiofrequency ablation using internally cooled wet electrodes in bipolar mode for the treatment of recurrent hepatocellular carcinoma after locoregional treatment: a randomized prospective comparative study. PLoS One. 2020;15:e0239733. [DOI] [PubMed] [PMC]

Ilagan CH, Goldman DA, Gönen M, Aveson VG, Babicky M, Balachandran VP, et al. Recurrence of hepatocellular carcinoma after complete radiologic response to trans-arterial embolization: a retrospective study on patterns, treatments, and prognoses. Ann Surg Oncol. 2022;29:6815–26. [DOI] [PubMed] [PMC]

Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, et al.; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:56–66. Erratum in: Lancet. 2017;389:36. [DOI] [PubMed]

Hu WY, Wei HY, Li KM, Wang RB, Xu XQ, Feng R. LINC00511 as a ceRNA promotes cell malignant behaviors and correlates with prognosis of hepatocellular carcinoma patients by modulating miR-195/EYA1 axis. Biomed Pharmacother. 2020;121:109642. [DOI] [PubMed]

Ma C, Kesarwala AH, Eggert T, Medina-Echeverz J, Kleiner DE, Jin P, et al. NAFLD causes selective CD4⁺ T lymphocyte loss and promotes hepatocarcinogenesis. Nature. 2016;531:253–7. [DOI] [PubMed] [PMC]

Mehal WZ. The Gordian Knot of dysbiosis, obesity and NAFLD. Nat Rev Gastroenterol Hepatol. 2013;10:637–44. [DOI] [PubMed]

Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380:1450–62. [DOI] [PubMed]

10.

Chen W, Desert R, Ge X, Han H, Song Z, Das S, et al. The matrisome genes from hepatitis B-related hepatocellular carcinoma unveiled. Hepatol Commun. 2021;5:1571–85. [DOI] [PubMed] [PMC]

11.

Behary J, Raposo AE, Amorim NML, Zheng H, Gong L, McGovern E, et al. Defining the temporal evolution of gut dysbiosis and inflammatory responses leading to hepatocellular carcinoma in Mdr2 -/- mouse model. BMC Microbiol. 2021;21:113. [DOI] [PubMed] [PMC]

12.

Ponziani FR, Bhoori S, Castelli C, Putignani L, Rivoltini L, Del Chierico F, et al. Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. Hepatology. 2019;69:107–20. [DOI] [PubMed]

13.

Zhang X, Coker OO, Chu ES, Fu K, Lau HCH, Wang YX, et al. Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites. Gut. 2021;70:761–74. [DOI] [PubMed] [PMC]

14.

Rezasoltani S, Yadegar A, Asadzadeh Aghdaei H, Reza Zali M. Modulatory effects of gut microbiome in cancer immunotherapy: a novel paradigm for blockade of immune checkpoint inhibitors. Cancer Med. 2021;10:1141–54. [DOI] [PubMed] [PMC]

15.

Wu Y, Zheng L. Dynamic education of macrophages in different areas of human tumors. Cancer Microenviron. 2012;5:195–201. [DOI] [PubMed] [PMC]

16.

Ahmed F, Steele JC, Herbert JM, Steven NM, Bicknell R. Tumor stroma as a target in cancer. Curr Cancer Drug Targets. 2008;8:447–53. [DOI] [PubMed]

17.

Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L, et al. Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol. 2009;50:980–9. [DOI] [PubMed]

18.

Zhao F, Hoechst B, Gamrekelashvili J, Ormandy LA, Voigtländer T, Wedemeyer H, et al. Human CCR4⁺ CCR6⁺ Th17 cells suppress autologous CD8⁺ T cell responses. J Immunol. 2012;188:6055–62. [DOI] [PubMed] [PMC]

19.

Liao R, Sun J, Wu H, Yi Y, Wang JX, He HW, et al. High expression of IL-17 and IL-17RE associate with poor prognosis of hepatocellular carcinoma. J Exp Clin Cancer Res. 2013;32:3. [DOI] [PubMed] [PMC]

20.

Kuang DM, Peng C, Zhao Q, Wu Y, Chen MS, Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells^†. Hepatology. 2010;51:154–64. [DOI] [PubMed]

21.

Michaelis L, Treß M, Löw HC, Klees J, Klameth C, Lange A, et al. Gut commensal-induced IκBζ expression in dendritic cells influences the Th17 response. Front Immunol. 2021;11:612336. [DOI] [PubMed] [PMC]

22.

Sung CY, Lee NP, El-Nezami H. Regulation of T helper 17 by bacteria: an approach for the treatment of hepatocellular carcinoma. Int J Hepatol. 2012;2012:439024. [DOI] [PubMed] [PMC]

23.

Gu FM, Li QL, Gao Q, Jiang JH, Zhu K, Huang XY, et al. IL-17 induces AKT-dependent IL-6/JAK2/STAT3 activation and tumor progression in hepatocellular carcinoma. Mol Cancer. 2011;10:150. [DOI] [PubMed] [PMC]

24.

Qin H, Yuan B, Huang W, Wang Y. Utilizing gut microbiota to improve hepatobiliary tumor treatments: recent advances. Front Oncol. 2022;12:924696. [DOI] [PubMed] [PMC]

25.

Mikó E, Vida A, Bai P. Translational aspects of the microbiome—to be exploited. Cell Biol Toxicol. 2016;32:153–6. [DOI] [PubMed]

26.

Kovács T, Mikó E, Vida A, Sebő É, Toth J, Csonka T, et al. Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors. Sci Rep. 2019;9:1300. [DOI] [PubMed] [PMC]

27.

Yu LX, Schwabe RF. The gut microbiome and liver cancer: mechanisms and clinical translation. Nat Rev Gastroenterol Hepatol. 2017;14:527–39. [DOI] [PubMed] [PMC]

28.

Wu L, Feng J, Li J, Yu Q, Ji J, Wu J, et al. The gut microbiome-bile acid axis in hepatocarcinogenesis. Biomed Pharmacother. 2021;133:111036. [DOI] [PubMed]

29.

Wang C, Yang M, Zhao J, Li X, Xiao X, Zhang Y, et al. Bile salt (glycochenodeoxycholate acid) induces cell survival and chemoresistance in hepatocellular carcinoma. J Cell Physiol. 2019;234:10899–906. [DOI] [PubMed]

30.

Xie G, Wang X, Huang F, Zhao A, Chen W, Yan J, et al. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis. Int J Cancer. 2016;139:1764–75. [DOI] [PubMed] [PMC]

31.

Ko CW, Qu J, Black DD, Tso P. Regulation of intestinal lipid metabolism: current concepts and relevance to disease. Nat Rev Gastroenterol Hepatol. 2020;17:169–83. [DOI] [PubMed]

32.

Ridlon JM, Harris SC, Bhowmik S, Kang DJ, Hylemon PB. Consequences of bile salt biotransformations by intestinal bacteria. Gut Microbes. 2016;7:22–39. Erratum in: Gut Microbes. 2016;7:262. [DOI] [PubMed] [PMC]

33.

Ramírez-Pérez O, Cruz-Ramón V, Chinchilla-López P, Méndez-Sánchez N. The role of the gut microbiota in bile acid metabolism. Ann Hepatol. 2017;16:S21–6. [DOI] [PubMed]

34.

Tsuei J, Chau T, Mills D, Wan YJ. Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer. Exp Biol Med (Maywood). 2014;239:1489–504. [DOI] [PubMed] [PMC]

35.

van Best N, Rolle-Kampczyk U, Schaap FG, Basic M, Olde Damink SWM, Bleich A, et al. Bile acids drive the newborn’s gut microbiota maturation. Nat Commun. 2020;11:3692. [DOI] [PubMed] [PMC]

36.

Thomas RM, Jobin C. The microbiome and cancer: is the ‘Oncobiome’ mirage real? Trends Cancer. 2015;1:24–35. [DOI] [PubMed] [PMC]

37.

Sipos A, Ujlaki G, Mikó E, Maka E, Szabó J, Uray K, et al. The role of the microbiome in ovarian cancer: mechanistic insights into oncobiosis and to bacterial metabolite signaling. Mol Med. 2021;27:33. [DOI] [PubMed] [PMC]

38.

Kiss B, Mikó E, Sebő É, Toth J, Ujlaki G, Szabó J, et al. Oncobiosis and microbial metabolite signaling in pancreatic adenocarcinoma. Cancers (Basel). 2020;12:1068. [DOI] [PubMed] [PMC]

39.

Ridlon JM, Devendran S, Alves JM, Doden H, Wolf PG, Pereira GV, et al. The ‘in vivo lifestyle’ of bile acid 7α-dehydroxylating bacteria: comparative genomics, metatranscriptomic, and bile acid metabolomics analysis of a defined microbial community in gnotobiotic mice. Gut Microbes. 2020;11:381–404. [DOI] [PubMed] [PMC]

40.

Vital M, Rud T, Rath S, Pieper DH, Schlüter D. Diversity of bacteria exhibiting bile acid-inducible 7α-dehydroxylation genes in the human gut. Comput Struct Biotechnol J. 2019;17:1016–9. [DOI] [PubMed] [PMC]

41.

Jia W, Xie G, Jia W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol. 2018;15:111–28. [DOI] [PubMed] [PMC]

42.

Zhang WJ, Chen SJ, Zhou SC, Wu SZ, Wang H. Inflammasomes and fibrosis. Front Immunol. 2021;12:643149. [DOI] [PubMed] [PMC]

43.

Degirolamo C, Modica S, Palasciano G, Moschetta A. Bile acids and colon cancer: solving the puzzle with nuclear receptors. Trends Mol Med. 2011;17:564–72. [DOI] [PubMed]

44.

Nguyen PT, Kanno K, Pham QT, Kikuchi Y, Kakimoto M, Kobayashi T, et al. Senescent hepatic stellate cells caused by deoxycholic acid modulates malignant behavior of hepatocellular carcinoma. J Cancer Res Clin Oncol. 2020;146:3255–68. [DOI] [PubMed]

45.

Zhang W, Zhou L, Yin P, Wang J, Lu X, Wang X, et al. A weighted relative difference accumulation algorithm for dynamic metabolomics data: long-term elevated bile acids are risk factors for hepatocellular carcinoma. Sci Rep. 2015;5:8984. [DOI] [PubMed] [PMC]

46.

Liu R, Li X, Hylemon PB, Zhou H. Conjugated bile acids promote invasive growth of esophageal adenocarcinoma cells and cancer stem cell expansion via sphingosine 1-phosphate receptor 2-mediated yes-associated protein activation. Am J Pathol. 2018;188:2042–58. [DOI] [PubMed] [PMC]

47.

Zhang Q, Agoston AT, Pham TH, Zhang W, Zhang X, Huo X, et al. Acidic bile salts induce epithelial to mesenchymal transition via VEGF signaling in non-neoplastic Barrett’s cells. Gastroenterology. 2019;156:130–44.E10. [DOI] [PubMed] [PMC]

48.

Matsuhisa T, Arakawa T, Watanabe T, Tokutomi T, Sakurai K, Okamura S, et al. Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: a multicenter study of 2283 cases. Dig Endosc. 2013;25:519–25. [DOI] [PubMed]

49.

Ni Z, Min Y, Han C, Yuan T, Lu W, Ashktorab H, et al. TGR5-HNF4α axis contributes to bile acid-induced gastric intestinal metaplasia markers expression. Cell Death Discov. 2020;6:56. [DOI] [PubMed] [PMC]

50.

Rees DO, Crick PJ, Jenkins GJ, Wang Y, Griffiths WJ, Brown TH, et al. Comparison of the composition of bile acids in bile of patients with adenocarcinoma of the pancreas and benign disease. J Steroid Biochem Mol Biol. 2017;174:290–5. [DOI] [PubMed] [PMC]

51.

Feng HY, Chen YC. Role of bile acids in carcinogenesis of pancreatic cancer: an old topic with new perspective. World J Gastroenterol. 2016;22:7463–77. [DOI] [PubMed] [PMC]

52.

Farhana L, Nangia-Makker P, Arbit E, Shango K, Sarkar S, Mahmud H, et al. Bile acid: a potential inducer of colon cancer stem cells. Stem Cell Res Ther. 2016;7:181. [DOI] [PubMed] [PMC]

53.

Hori T, Matsumoto K, Sakaitani Y, Sato M, Morotomi M. Effect of dietary deoxycholic acid and cholesterol on fecal steroid concentration and its impact on the colonic crypt cell proliferation in azoxymethane-treated rats. Cancer Lett. 1998;124:79–84. [DOI] [PubMed]

54.

Donisi C, Puzzoni M, Ziranu P, Lai E, Mariani S, Saba G, et al. Immune checkpoint inhibitors in the treatment of HCC. Front Oncol. 2021;10:601240. [DOI] [PubMed] [PMC]

55.

Lai E, Astara G, Ziranu P, Pretta A, Migliari M, Dubois M, et al. Introducing immunotherapy for advanced hepatocellular carcinoma patients: too early or too fast? Crit Rev Oncol Hematol. 2021;157:103167. [DOI] [PubMed]

56.

Greten TF, Lai CW, Li G, Staveley-O’Carroll KF. Targeted and immune-based therapies for hepatocellular carcinoma. Gastroenterology. 2019;156:510–24. [DOI] [PubMed] [PMC]

57.

Katariya NN, Lizaola-Mayo BC, Chascsa DM, Giorgakis E, Aqel BA, Moss AA, et al. Immune checkpoint inhibitors as therapy to down-stage hepatocellular carcinoma prior to liver transplantation. Cancers (Basel). 2022;14:2056. [DOI] [PubMed] [PMC]

58.

Abdelrahim M, Esmail A, Saharia A, Abudayyeh A, Abdel-Wahab N, Diab A, et al. Utilization of immunotherapy for the treatment of hepatocellular carcinoma in the peri-transplant setting: transplant oncology view. Cancers (Basel). 2022;14:1760. [DOI] [PubMed] [PMC]

59.

Hewitt DB, Rahnemai-Azar AA, Pawlik TM. Potential experimental immune checkpoint inhibitors for the treatment of cancer of the liver. Expert Opin Investig Drugs. 2021;30:827–35. [DOI] [PubMed]

60.

Zhang Y, Liu Z, Tian M, Hu X, Wang L, Ji J, et al. The altered PD-1/PD-L1 pathway delivers the ‘one-two punch’ effects to promote the Treg/Th17 imbalance in pre-eclampsia. Cell Mol Immunol. 2018;15:710–23. [DOI] [PubMed] [PMC]

61.

Kim ST, Chu Y, Misoi M, Suarez-Almazor ME, Tayar JH, Lu H, et al. Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy. Nat Commun. 2022;13:1970. [DOI] [PubMed] [PMC]

62.

Okiyama N, Tanaka R. Immune-related adverse events in various organs caused by immune checkpoint inhibitors. Allergol Int. 2022;71:169–78. [DOI] [PubMed]

63.

Li S, Na R, Li X, Zhang Y, Zheng T. Targeting interleukin-17 enhances tumor response to immune checkpoint inhibitors in colorectal cancer. Biochim Biophys Acta Rev Cancer. 2022;1877:188758. [DOI] [PubMed]

64.

Ramesh R, Kozhaya L, McKevitt K, Djuretic IM, Carlson TJ, Quintero MA, et al. Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids. J Exp Med. 2014;211:89–104. [DOI] [PubMed] [PMC]

65.

Melin A, Routier É, Roy S, Pradere P, Le Pavec J, Pierre T, et al. Sarcoid-like granulomatosis associated with immune checkpoint inhibitors in melanoma. Cancers (Basel). 2022;14:2937. [DOI] [PubMed] [PMC]

66.

Downs-Canner S, Berkey S, Delgoffe GM, Edwards RP, Curiel T, Odunsi K, et al. Suppressive IL-17A⁺Foxp3⁺ and ex-Th17 IL-17A^negFoxp3⁺ T_reg cells are a source of tumour-associated T_reg cells. Nat Commun. 2017;8:14649. [DOI] [PubMed] [PMC]

67.

Saenz SA, Local A, Carr T, Shakya A, Koul S, Hu H, et al. Small molecule allosteric inhibitors of RORγt block Th17-dependent inflammation and associated gene expression in vivo. PLoS One. 2021;16:e0248034. [DOI] [PubMed] [PMC]

68.

Kendall T, Verheij J, Gaudio E, Evert M, Guido M, Goeppert B, et al. Anatomical, histomorphological and molecular classification of cholangiocarcinoma. Liver Int. 2019;39:7–18. [DOI] [PubMed]

69.

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;7:193. [DOI] [PubMed] [PMC]

70.

Nomura M, Nagatomo R, Doi K, Shimizu J, Baba K, Saito T, et al. Association of short-chain fatty acids in the gut microbiome with clinical response to treatment with nivolumab or pembrolizumab in patients with solid cancer tumors. JAMA Netw Open. 2020;3:e202895. [DOI] [PubMed] [PMC]

71.

Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103. [DOI] [PubMed] [PMC]

72.

Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–7. [DOI] [PubMed]

73.

Schwabe RF, Greten TF. Gut microbiome in HCC-mechanisms, diagnosis and therapy. J Hepatol. 2020;72:230–8. [DOI] [PubMed]

74.

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;350:1084–9. [DOI] [PubMed] [PMC]

75.

Pierrard J, Seront E. Impact of the gut microbiome on immune checkpoint inhibitor efficacy—a systematic review. Curr Oncol. 2019;26:395–403. [DOI] [PubMed] [PMC]

76.

Li J, Sung CY, Lee N, Ni Y, Pihlajamäki J, Panagiotou G, et al. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci U S A. 2016;113:E1306–15. [DOI] [PubMed] [PMC]

77.

Lee NY, Suk KT. The role of the gut microbiome in liver cirrhosis treatment. Int J Mol Sci. 2021;22:199. [DOI] [PubMed] [PMC]

78.

Huang H, Ren Z, Gao X, Hu X, Zhou Y, Jiang J, et al. Integrated analysis of microbiome and host transcriptome reveals correlations between gut microbiota and clinical outcomes in HBV-related hepatocellular carcinoma. Genome Med. 2020;12:102. [DOI] [PubMed] [PMC]

79.

Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10^-/- mice. Nature. 2012;487:104–8. [DOI] [PubMed] [PMC]

80.

Behary J, Amorim N, Jiang XT, Raposo A, Gong L, McGovern E, et al. Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma. Nat Commun. 2021;12:187. [DOI] [PubMed] [PMC]

81.

Lee PC, Wu CJ, Hung YW, Lee CJ, Chi CT, Lee IC, et al. Gut microbiota and metabolites associate with outcomes of immune checkpoint inhibitor–treated unresectable hepatocellular carcinoma. J Immunother Cancer. 2022;10:e004779. [DOI] [PubMed] [PMC]

82.

MaruYama T, Kobayashi S, Shibata H, Chen W, Owada Y. Curcumin analog GO-Y030 boosts the efficacy of anti-PD-1 cancer immunotherapy. Cancer Sci. 2021;112:4844–52. [DOI] [PubMed] [PMC]

83.

Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al.; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–905. [DOI] [PubMed]

84.

Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76:681–93. [DOI] [PubMed] [PMC]

85.

Jiang X, Zheng J, Zhang S, Wang B, Wu C, Guo X. Advances in the involvement of gut microbiota in pathophysiology of NAFLD. Front Med (Lausanne). 2020;7:361. [DOI] [PubMed] [PMC]

86.

Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017;14:356–65. [DOI] [PubMed]

87.

Hebeda CB, Pinedo FJ, Bolonheis SM, Ferreira ZF, Muscará MN, Teixeira SA, et al. Intracellular mechanisms of hydroquinone toxicity on endotoxin-activated neutrophils. Arch Toxicol. 2012;86:1773–81. [DOI] [PubMed]

88.

Liu H, Wang J, Lin J, Sun J, Guo J, Liu Z, et al. LPS induced PCT production via TLR-4/NF-кB passway:it is the difference of G-/G+ bacteremia rats. Cytokine. 2021;137:155317. [DOI] [PubMed]

89.

Gao S, Chen T, Li L, Liu X, Liu Y, Zhao J, et al. Hypoxia-inducible ubiquitin specific peptidase 13 contributes to tumor growth and metastasis via enhancing the toll-like receptor 4/myeloid differentiation primary response gene 88/nuclear factor-κB pathway in hepatocellular carcinoma. Front Cell Dev Biol. 2020;8:587389. [DOI] [PubMed] [PMC]

90.

Xie L, Huang Z, Meng H, Shi X, Xie J. Immunomodulation effect of polysaccharides from liquid fermentation of Monascus purpureus 40269 via membrane TLR-4 to activate the MAPK and NF-κB signaling pathways. Int J Biol Macromol. 2022;201:480–91. [DOI] [PubMed]

91.

Ikeda Y, Taniguchi K, Yoshikawa S, Sawamura H, Tsuji A, Matsuda S. A budding concept with certain microbiota, anti-proliferative family proteins, and engram theory for the innovative treatment of colon cancer. Explor Med. 2022;3:468–78. [DOI]

92.

Chu H, Williams B, Schnabl B. Gut microbiota, fatty liver disease, and hepatocellular carcinoma. Liver Res. 2018;2:43–51. [DOI] [PubMed] [PMC]

93.

Mukaida N. Intestinal microbiota: unexpected alliance with tumor therapy. Immunotherapy. 2014;6:231–3. [DOI] [PubMed]

94.

Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342:967–70. [DOI] [PubMed] [PMC]

95.

Kou Y, Zheng X, Meng L, Liu M, Xu S, Jing Q, et al. The HVEM-BTLA immune checkpoint restrains murine chronic cholestatic liver injury by regulating the gut microbiota. Front Immunol. 2022;13:773341. [DOI] [PubMed] [PMC]

96.

Hang S, Paik D, Yao L, Kim E, Trinath J, Lu J, et al. Bile acid metabolites control T_H17 and T_regcell differentiation. Nature. 2019;576:143–8. Erratum in: Nature. 2020;579:E7. [DOI] [PubMed] [PMC]

97.

Campbell C, McKenney PT, Konstantinovsky D, Isaeva OI, Schizas M, Verter J, et al. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature. 2020;581:475–9. [DOI] [PubMed] [PMC]

98.

Guo S, Li K, Hu B, Li C, Zhang M, Hussain A, et al. Membrane-destabilizing ionizable lipid empowered imaging-guided siRNA delivery and cancer treatment. Exploration (Beijing). 2021;1:35–49. [DOI] [PubMed] [PMC]

99.

Wu M, Shi K, Huang R, Liu C, Yin L, Yong W, et al. Facile preparation of ¹⁷⁷Lu-microspheres for hepatocellular carcinoma radioisotope therapy. Chin Chem Lett. 2022;33:3492–6. [DOI]

100.

Chen H, Teng M, Zhang H, Liang X, Cheng H, Liu G, et al. Advanced radionuclides in diagnosis and therapy for hepatocellular carcinoma. Chin Chem Lett. 2022;33:3371–83. [DOI]

101.

Miller PL, Carson TL. Mechanisms and microbial influences on CTLA-4 and PD-1-based immunotherapy in the treatment of cancer: a narrative review. Gut Pathog. 2020;12:43. [DOI] [PubMed] [PMC]