Discovery of a Metastatic Immune Escape Mechanism Initiated by the Loss of Expression of the Tumour Biomarker Interleukin-33.
A new paradigm for understanding immune-surveillance and immune escape in cancer is described here. Metastatic carcinomas express reduced levels of IL-33 and diminished levels of antigen processing machinery (APM), compared to syngeneic primary tumours. Complementation of IL-33 expression in metastatic tumours upregulates APM expression and functionality of major histocompatibility complex (MHC)-molecules, resulting in reduced tumour growth rates and a lower frequency of circulating tumour cells. Parallel studies in humans demonstrate that low tumour expression of IL-33 is an immune biomarker associated with recurrent prostate and kidney renal clear cell carcinomas. Thus, IL-33 has a significant role in cancer immune-surveillance against primary tumours, which is lost during the metastatic transition that actuates immune escape in cancer.
The Michael Smith Laboratories, University of British Columbia, 301-2185 East Mall, Vancouver, BC Canada V6T 1Z4.|Department of Microbiology &Immunology, University of British Columbia, 1365 - 2350 Health Sciences Mall, Vancouver, BC Canada V6T 1Z3.
Iryna
I
Saranchova
The Michael Smith Laboratories, University of British Columbia, 301-2185 East Mall, Vancouver, BC Canada V6T 1Z4.|Department of Microbiology &Immunology, University of British Columbia, 1365 - 2350 Health Sciences Mall, Vancouver, BC Canada V6T 1Z3.
Jeffrey
J
Han
The Michael Smith Laboratories, University of British Columbia, 301-2185 East Mall, Vancouver, BC Canada V6T 1Z4.|Department of Microbiology &Immunology, University of British Columbia, 1365 - 2350 Health Sciences Mall, Vancouver, BC Canada V6T 1Z3.
Hui
H
Huang
The Michael Smith Laboratories, University of British Columbia, 301-2185 East Mall, Vancouver, BC Canada V6T 1Z4.|Department of Microbiology &Immunology, University of British Columbia, 1365 - 2350 Health Sciences Mall, Vancouver, BC Canada V6T 1Z3.
Franz
F
Fenninger
The Michael Smith Laboratories, University of British Columbia, 301-2185 East Mall, Vancouver, BC Canada V6T 1Z4.
Kyung Bok
KB
Choi
The Michael Smith Laboratories, University of British Columbia, 301-2185 East Mall, Vancouver, BC Canada V6T 1Z4.
Lonna
L
Munro
The Michael Smith Laboratories, University of British Columbia, 301-2185 East Mall, Vancouver, BC Canada V6T 1Z4.
Cheryl
C
Pfeifer
Department of Animal Care Services, University of British Columbia, 4145 Wesbrook Mall, Vancouver BC Canada V6T 1W5.
Ian
I
Welch
Department of Urologic Sciences, University of British Columbia Gordon &Leslie Diamond Health Care Centre, Level 6, 2775 Laurel Street, Vancouver, BC Canada V5Z 1M9.|The Vancouver Prostate Centre, University of British Columbia 2660 Oak Street, Vancouver, BC Canada V6H 3Z6.
Alexander W
AW
Wyatt
Department of Urologic Sciences, University of British Columbia Gordon &Leslie Diamond Health Care Centre, Level 6, 2775 Laurel Street, Vancouver, BC Canada V5Z 1M9.|The Vancouver Prostate Centre, University of British Columbia 2660 Oak Street, Vancouver, BC Canada V6H 3Z6.
Ladan
L
Fazli
Department of Urologic Sciences, University of British Columbia Gordon &Leslie Diamond Health Care Centre, Level 6, 2775 Laurel Street, Vancouver, BC Canada V5Z 1M9.|The Vancouver Prostate Centre, University of British Columbia 2660 Oak Street, Vancouver, BC Canada V6H 3Z6.
Martin E
ME
Gleave
The Michael Smith Laboratories, University of British Columbia, 301-2185 East Mall, Vancouver, BC Canada V6T 1Z4.|Department of Microbiology &Immunology, University of British Columbia, 1365 - 2350 Health Sciences Mall, Vancouver, BC Canada V6T 1Z3.|Department of Medical Genetics, University of British Columbia 1364 - 2350 Health Sciences Mall, Vancouver, BC Canada V6T 1Z3.|Department of Zoology, University of British Columbia 4200 - 6270 University Blvd, Vancouver, BC Canada V6T 1Z4.|Centre for Blood Research at the University of British Columbia 4th Floor - 2350 Health Sciences Mall, Vancouver, BC Canada V6T 1Z3.|Djavad Mowafaghian Centre for Brain Health at the University of British Columbia 2215 Wesbrook Mall, Vancouver BC Canada V6T 1Z3.
Wilfred A
WA
Jefferies
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D000067596:Interleukin-33 / Q000235:genetics* / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology*; D019139:Tumor Escape
D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; C506536:IL33 protein, human; D000067596:Interleukin-33