BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis.
BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR=0.651, p=0.006 and HR=0.642, p=0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR=1.355 p=0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
Cécile
C
Le Page
Alexandre
A
Marineau
Patrick K
PK
Bonza
Kurosh
K
Rahimi
Louis
L
Cyr
Ingrid
I
Labouba
Jason
J
Madore
Nathalie
N
Delvoye
Anne-Marie
AM
Mes-Masson
Diane M
DM
Provencher
Jean-François
JF
Cailhier
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015153:Blotting, Western; D000071797:Butyrophilins; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D037181:Lectins, C-Type / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism* / Q000473:pathology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis / Q000706:statistics & numerical data; D014162:Transfection; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000071797:Butyrophilins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; C576586:BTN3A2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule