Profound elevation of CD8+ T cells expressing the intraepithelial lymphocyte marker CD103 (alphaE/beta7 Integrin) in high-grade serous ovarian cancer.
BACKGROUND
Tumor-infiltrating CD8(+) T cells are strongly associated with survival in high-grade serous ovarian cancer, but their functional phenotype remains poorly defined. The mucosal integrin CD103 (alpha(E)/beta(7)) facilitates the infiltration of T cells into epithelial tissues, including gut and lung mucosa, solid organ allografts, and various epithelial cancers. We reasoned that CD103 might also be expressed by tumor-reactive T cells in ovarian cancer.


METHODS
Flow cytometry was used to assess the frequency and phenotype of CD103-expressing T cells in primary ascites fluid from 13 patients with high-grade serous ovarian cancer and 2 patients with recurrent disease.


RESULTS
We report that a subset of patients with advanced serous ovarian cancer have profoundly elevated frequencies of CD103-expressing CD8(+) cells in ascites (between 20% and 70% of CD8(+) cells in ascites were CD103(+)) and that CD103 expression correlated with levels of TGF-beta in ascitic fluid. Conversely, CD103 was not expressed on CD4(+) cells, even in those patients with very high frequencies of CD8(+)CD103(+) cells. CD8(+)CD103(+) cells were antigen-experienced (CD45RA(-)CD45RO(+)CD62L(lo)CCR7(-)) and of an intermediate (EM2) effector memory phenotype (CD27(+)CD28(-)). TCR repertoire analysis indicated significant skewing between CD8(+)CD103(-) and CD8(+)CD103(+) T cell subsets, suggesting the two populations contain distinct antigenic specificities. Lastly, HLA pentamer analysis revealed that one patient in the cohort harbored a high frequency of CD8(+) T cells in ascites that were specific for the tumor antigen NY-ESO-1, and that approximately 75% of these NY-ESO-1 specific CD8(+) T cells were CD103(+).


CONCLUSIONS
CD103(+) may be a marker of activated and tumor-reactive CD8(+) T cells in high-grade serous ovarian cancer.
Webb
John R
JR
Trev and Joyce Deeley Research Centre, BC Cancer Agency, Victoria, BC, Canada. jwebb@bccancer.bc.ca
Wick
Darin A
DA
Nielsen
Julie S
JS
Tran
Eric
E
Milne
Katy
K
McMurtrie
Elissa
E
Nelson
Brad H
BH
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D001201:Ascites / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D039001:Integrin alpha Chains / Q000096:biosynthesis / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D039001:Integrin alpha Chains; D008565:Membrane Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C091367:alpha E integrins