Preferential in situ CD4+CD56+ T cell activation and expansion within human glioblastoma.
Recent evidence suggests that suppression of the cellular immune response is often attributable to populations of functionally distinct T cells that act to down-regulate Ag-specific effector T cells. Using flow cytometry, we evaluated tumor-infiltrating lymphocytes (TIL) from patients undergoing neurosurgical resection of glioblastoma multiforme (GBM), metastatic lung carcinoma, and meningioma for markers known to be expressed on immunoregulatory T cells. Ex vivo phenotypic characteristics, cellular proliferation, and cytokine expression patterns were compared between T cell subsets found in the PBMC and within TIL from fresh tumor samples. Interestingly, nearly half of all T cells infiltrating GBM specimens were CD56(+) T cells, while much smaller percentages of similar cells were identified within metastatic lung tumors and meningiomas. CD56(+) T cells identified within GBM were not canonical, or "invariant," NKT cells, as they demonstrated diverse TCR expression, a primarily CD4 single-positive phenotype, and lack of CD1d reactivity. The percentage of CD56(+) T cells exhibiting evidence of proliferation within GBM was 3- to 4-fold higher than the proportion of proliferating CD56(-) T cells from these lesions. In addition, direct ex vivo analysis of cytokine expression by TIL from GBM demonstrated significant numbers of IL-4/IL-13 positive cells, cytokines that are integral in the cell-mediated repression of tumor immunity in experimental models. We propose that GBM has a unique capacity to recruit and activate CD4(+)CD56(+) T cells, a population that has not been previously described within human tumors.
Waziri
Allen
A
Department of Neurological Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. aew2001@columbia.edu
Killory
Brendan
B
Ogden
Alfred T
AT
Canoll
Peter
P
Anderson
Richard C E
RC
Kent
Sally C
SC
Anderson
David E
DE
Bruce
Jeffrey N
JN
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019002:CD56 Antigen / Q000032:analysis; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005909:Glioblastoma / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008579:Meningioma / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D019002:CD56 Antigen; D016207:Cytokines