The immune signature of CD8(+)CCR7(+) T cells in the peripheral circulation associates with disease recurrence in patients with HNSCC.
OBJECTIVE
Patients with cancer have an increased frequency of circulating apoptosis-sensitive CD8(+)CCR7(neg) T cells and few CD8(+)CCR7(+) T cells versus normal controls. The functional and clinical significance of this imbalance was investigated using peripheral blood of patients with squamous cell carcinoma of the head and neck (HNSCC).


METHODS
The frequency of circulating CD8(+) T cells co-expressing CCR7, CD45RO, CD28, and Annexin V (ANXV) was evaluated in 67 patients and 57 normal controls by flow cytometry. Spearman rank correlations among immunophenotypic profiles were analyzed. Recursive partitioning classified subjects as patients or normal controls based on CD8(+)CCR7(+) T-cell percentages. Kaplan-Meier plots estimated disease-free survival (DFS).


RESULTS
The CD8(+)CCR7(+) T-cell frequency was low, whereas that of total CD8(+)CCR7(neg) and ANXV-binding CD8(+)CCR7(neg) T cells was higher in patients with HNSCC than in normal controls (P < 0.001-0.0001). ANXV binding correlated with the absence of CCR7 on CD8(+) T cells (P < 0.001). ANXV binding was negatively correlated with the CD8(+)CD45RO(neg)CCR7(+) (T(N)) cell frequency (P < 0.01) but positively correlated (P < 0.01) with that of CD8(+)CD45RO(+)CCR7(+) (T(CM)) T cells and of the two CCR7(neg) subsets (T(PM) and T(TD)). In recursive partitioning models, the CD8(+)CCR7(+) T-cell frequency of 31% distinguished patients from normal controls with 77% to 88% accuracy after cross-validation. In 25 patients tested before any therapy, the CD8(+)CCR7(+) T-cell frequency of less than 28% predicted disease recurrence within 4 years of definitive therapy (P < 0.0115).


CONCLUSIONS
The CD8(+)CCR7(+) T-cell frequency in HNSCC patients' blood tested at diagnosis can discriminate them from normal controls and predicts disease recurrence.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Malgorzata
M
Czystowska
William
W
Gooding
Miroslaw J
MJ
Szczepanski
Andres
A
Lopez-Abaitero
Robert L
RL
Ferris
Jonas T
JT
Johnson
Theresa L
TL
Whiteside
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D018106:CD28 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000097:blood*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000097:blood*; D000077195:Squamous Cell Carcinoma of Head and Neck
D017304:Annexin A5; C515370:CCR7 protein, human; D018106:CD28 Antigens; D016827:CD8 Antigens; D054400:Receptors, CCR7; D017493:Leukocyte Common Antigens