Research progress of IgG4 and cancer immunity_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CUI Ming ,  LIAO Quan , ZHAO Yupei

Department of General Surgery, Peking Union Medical College Hospital, Translational Medical Center of Peking Union Medical College, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, P.R.China;

Corresponding author：

LIAO Quan, Email: lqpumc@126.com

Keywords：

immunoglobulin G4; cancer immunity; cancer; IgG4-related disease

DOI：

10.7507/1007-9424.201702052

Video：

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Objective To elucidate current research status of immunoglobulin G4 (IgG4) and cancer immunity. Method The relevant literatures of relationship between IgG4 and cancer immunity were collected and reviewed. Results The IgG4 high-level and the intratumoral infiltration of the IgG4-positive plasma cells were the predictors for a worse prognosis in the cancer patients. The relationship between the serum IgG4 level and the prognosis in the cancer patients was unclear. The IgG4 related immunity might contribute to the tumor-associated escape from the immune surveillance. Conclusions Recent studies implicate that IgG4 might play a role in tumor progression. Specific mechanisms for IgG4 in tumor immune microenvironment need to be further explored. Dissecting relationship between IgG4 and cancer immunity might provide a novel idea for cancer therapy.

Citation： CUI Ming, LIAO Quan, ZHAO Yupei. Research progress of IgG4 and cancer immunity. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(8): 1021-1024. doi: 10.7507/1007-9424.201702052 Copy

1.	Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674.
2.	Vesely MD, Kershaw MH, Schreiber RD, et al. Natural innate and adaptive immunity to cancer. Annu Rev Immunol, 2011, 29: 235-271.
3.	Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity, 2013, 39(1): 1-10.
4.	Zitvogel L, Kroemer G. Cancer: Antibodies regulate antitumour immunity. Nature, 2015, 521(7550): 35-37.
5.	Schur PH. IgG subclasses. A historical perspective. Monogr Allergy, 1988, 23: 1-11.
6.	Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol, 2014, 5: 520.
7.	Crescioli S, Correa I, Karagiannis P, et al. IgG4 characteristics and functions in cancer immunity. Curr Allergy Asthma Rep, 2016, 16(1): 7.
8.	Sibéril S, Dutertre CA, Boix C, et al. Molecular aspects of human FcγR interactions with IgG: functional and therapeutic consequences. Immunol Lett, 2006, 106(2): 111-118.
9.	Karsten CM, Köhl J. The immunoglobulin, IgG Fc receptor and complement triangle in autoimmune diseases. Immunobiology, 2012, 217(11): 1067-1079.
10.	Rayner LE, Hui GK, Gor J, et al. The Fab conformations in the solution structure of human immunoglobulin G4 (IgG4) restrict access to its Fc region: implications for functional activity. J Biol Chem, 2014, 289(30): 20740-20756.
11.	Tan L K, Shopes R J, Oi V T, et al. Influence of the hinge region on complement activation, C1q binding, and segmental flexibility in chimeric human immunoglobulins. Proc Natl Acad Sci USA, 1990, 87(1): 162-166.
12.	Davies AM, Sutton BJ. Human IgG4: a structural perspective. Immunol Rev, 2015, 268(1): 139-159.
13.	Davies AM, Rispens T, Ooijevaar-De HP, et al. Structural determinants of unique properties of human IgG4-Fc. J Mol Biol, 2014, 426(3): 630-644.
14.	Broug E, Bland-Ward P A, Powell J, et al. Fab-arm exchange. Nat Biotechnol, 2010, 28(2): 123-126.
15.	Aalberse R C, Schuurman J. IgG4 breaking the rules. Immunology, 2002, 105(1): 9-19.
16.	Labrijn AF, Buijsse AO, van den Bremer ET, et al. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo. Nat Biotechnol, 2009, 27(8): 767-771.
17.	Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med, 2001, 344(10): 732-738.
18.	Kamisawa T, Zen Y, Pillai S, et al. IgG4-related disease. Lancet, 2015, 385(9976): 1460-1471.
19.	Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
20.	Ghazale A, Chari S. Is autoimmune pancreatitis a risk factor for pancreatic cancer? Pancreas, 2007, 35(4): 376.
21.	Inoue H, Miyatani H, Sawada Y, et al. A case of pancreas cancer with autoimmune pancreatitis. Pancreas, 2006, 33(2): 208-209.
22.	Witkiewicz AK, Kennedy EP, Kennyon L, et al. Synchronous autoimmune pancreatitis and infiltrating pancreatic ductal adenocarcinoma: case report and review of the literature. Hum Pathol, 2008, 39(10): 1548-1551.
23.	Chandrasegaram MD, Chiam SC, Nguyen NQ, et al. A case of pancreatic cancer in the setting of autoimmune pancreatitis with nondiagnostic serum markers. Case Rep Surg, 2013, 2013: 809023.
24.	Fukui T, Mitsuyama T, Takaoka M, et al. Pancreatic cancer associated with autoimmune pancreatitis in remission. Intern Med, 2008, 47(3): 151-155.
25.	Pezzilli R, Vecchiarelli S, Di Marco MC, et al. Pancreatic ductal adenocarcinoma associated with autoimmune pancreatitis. Case Rep Gastroenterol, 2011, 5(2): 378-385.
26.	Gupta R, Khosroshahi A, Shinagare S, et al. Does autoimmune pancreatitis increase the risk of pancreatic carcinoma? a retrospective analysis of pancreatic resections. Pancreas, 2013, 42(3): 506-510.
27.	Ngwa T, Law R, Hart P, et al. Serum IgG4 elevation in pancreatic cancer: diagnostic and prognostic significance and association with autoimmune pancreatitis. Pancreas, 2015, 44(4): 557-560.
28.	Hart PA, Law RJ, Dierkhising RA, et al. Risk of cancer in autoimmune pancreatitis: a case-control study and review of the literature. Pancreas, 2014, 43(3): 417-421.
29.	Fragoulis GE, Moutsopoulos HM. IgG4 syndrome: old disease, new perspective. J Rheumatol, 2010, 37(7): 1369-1370.
30.	Elinav E, Nowarski R, Thaiss CA, et al. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer, 2013, 13(11): 759-771.
31.	Fremd C, Schuetz F, Sohn C, et al. B cell-regulated immune responses in tumor models and cancer patients. Oncoimmunology, 2013, 2(7): e25443.
32.	Karagiannis P, Gilbert AE, Josephs DH, et al. IgG4 subclass antibodies impair antitumor immunity in melanoma. J Clin Invest, 2013, 123(4): 1457-1474.
33.	Liu Q, Niu Z, Li Y, et al. Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection. Cancer Immunol Immunother, 2016, 65(8): 931-940.
34.	Harada K, Shimoda S, Kimura Y, et al. Significance of immunoglobulin G4 (IgG4)-positive cells in extrahepatic cholangiocarcinoma: molecular mechanism of IgG4 reaction in cancer tissue. Hepatology, 2012, 56(1): 157-164.
35.	Miyatani K, Saito H, Murakami Y, et al. A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis. Virchows Arch, 2016, 468(5): 549-557.
36.	Karagiannis P, Villanova F, Josephs DH, et al. Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma. Oncoimmunology, 2015, 4(11): e1032492.
37.	Mielgo A, Schmid M C. Impact of tumour associated macrophages in pancreatic cancer. BMB Rep, 2013, 46(3): 131-138.

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674.
2. Vesely MD, Kershaw MH, Schreiber RD, et al. Natural innate and adaptive immunity to cancer. Annu Rev Immunol, 2011, 29: 235-271.
3. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity, 2013, 39(1): 1-10.
4. Zitvogel L, Kroemer G. Cancer: Antibodies regulate antitumour immunity. Nature, 2015, 521(7550): 35-37.
5. Schur PH. IgG subclasses. A historical perspective. Monogr Allergy, 1988, 23: 1-11.
6. Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol, 2014, 5: 520.
7. Crescioli S, Correa I, Karagiannis P, et al. IgG4 characteristics and functions in cancer immunity. Curr Allergy Asthma Rep, 2016, 16(1): 7.
8. Sibéril S, Dutertre CA, Boix C, et al. Molecular aspects of human FcγR interactions with IgG: functional and therapeutic consequences. Immunol Lett, 2006, 106(2): 111-118.
9. Karsten CM, Köhl J. The immunoglobulin, IgG Fc receptor and complement triangle in autoimmune diseases. Immunobiology, 2012, 217(11): 1067-1079.
10. Rayner LE, Hui GK, Gor J, et al. The Fab conformations in the solution structure of human immunoglobulin G4 (IgG4) restrict access to its Fc region: implications for functional activity. J Biol Chem, 2014, 289(30): 20740-20756.
11. Tan L K, Shopes R J, Oi V T, et al. Influence of the hinge region on complement activation, C1q binding, and segmental flexibility in chimeric human immunoglobulins. Proc Natl Acad Sci USA, 1990, 87(1): 162-166.
12. Davies AM, Sutton BJ. Human IgG4: a structural perspective. Immunol Rev, 2015, 268(1): 139-159.
13. Davies AM, Rispens T, Ooijevaar-De HP, et al. Structural determinants of unique properties of human IgG4-Fc. J Mol Biol, 2014, 426(3): 630-644.
14. Broug E, Bland-Ward P A, Powell J, et al. Fab-arm exchange. Nat Biotechnol, 2010, 28(2): 123-126.
15. Aalberse R C, Schuurman J. IgG4 breaking the rules. Immunology, 2002, 105(1): 9-19.
16. Labrijn AF, Buijsse AO, van den Bremer ET, et al. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo. Nat Biotechnol, 2009, 27(8): 767-771.
17. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med, 2001, 344(10): 732-738.
18. Kamisawa T, Zen Y, Pillai S, et al. IgG4-related disease. Lancet, 2015, 385(9976): 1460-1471.
19. Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
20. Ghazale A, Chari S. Is autoimmune pancreatitis a risk factor for pancreatic cancer? Pancreas, 2007, 35(4): 376.
21. Inoue H, Miyatani H, Sawada Y, et al. A case of pancreas cancer with autoimmune pancreatitis. Pancreas, 2006, 33(2): 208-209.
22. Witkiewicz AK, Kennedy EP, Kennyon L, et al. Synchronous autoimmune pancreatitis and infiltrating pancreatic ductal adenocarcinoma: case report and review of the literature. Hum Pathol, 2008, 39(10): 1548-1551.
23. Chandrasegaram MD, Chiam SC, Nguyen NQ, et al. A case of pancreatic cancer in the setting of autoimmune pancreatitis with nondiagnostic serum markers. Case Rep Surg, 2013, 2013: 809023.
24. Fukui T, Mitsuyama T, Takaoka M, et al. Pancreatic cancer associated with autoimmune pancreatitis in remission. Intern Med, 2008, 47(3): 151-155.
25. Pezzilli R, Vecchiarelli S, Di Marco MC, et al. Pancreatic ductal adenocarcinoma associated with autoimmune pancreatitis. Case Rep Gastroenterol, 2011, 5(2): 378-385.
26. Gupta R, Khosroshahi A, Shinagare S, et al. Does autoimmune pancreatitis increase the risk of pancreatic carcinoma? a retrospective analysis of pancreatic resections. Pancreas, 2013, 42(3): 506-510.
27. Ngwa T, Law R, Hart P, et al. Serum IgG4 elevation in pancreatic cancer: diagnostic and prognostic significance and association with autoimmune pancreatitis. Pancreas, 2015, 44(4): 557-560.
28. Hart PA, Law RJ, Dierkhising RA, et al. Risk of cancer in autoimmune pancreatitis: a case-control study and review of the literature. Pancreas, 2014, 43(3): 417-421.
29. Fragoulis GE, Moutsopoulos HM. IgG4 syndrome: old disease, new perspective. J Rheumatol, 2010, 37(7): 1369-1370.
30. Elinav E, Nowarski R, Thaiss CA, et al. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer, 2013, 13(11): 759-771.
31. Fremd C, Schuetz F, Sohn C, et al. B cell-regulated immune responses in tumor models and cancer patients. Oncoimmunology, 2013, 2(7): e25443.
32. Karagiannis P, Gilbert AE, Josephs DH, et al. IgG4 subclass antibodies impair antitumor immunity in melanoma. J Clin Invest, 2013, 123(4): 1457-1474.
33. Liu Q, Niu Z, Li Y, et al. Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection. Cancer Immunol Immunother, 2016, 65(8): 931-940.
34. Harada K, Shimoda S, Kimura Y, et al. Significance of immunoglobulin G4 (IgG4)-positive cells in extrahepatic cholangiocarcinoma: molecular mechanism of IgG4 reaction in cancer tissue. Hepatology, 2012, 56(1): 157-164.
35. Miyatani K, Saito H, Murakami Y, et al. A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis. Virchows Arch, 2016, 468(5): 549-557.
36. Karagiannis P, Villanova F, Josephs DH, et al. Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma. Oncoimmunology, 2015, 4(11): e1032492.
37. Mielgo A, Schmid M C. Impact of tumour associated macrophages in pancreatic cancer. BMB Rep, 2013, 46(3): 131-138.

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Research progress of IgG4 and cancer immunity

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