Tumor-Infiltrating Lymphocytes in Patients WIth Glioblastoma Multiforme Contain Oligoclonal Populations of T-Cells

TUMOR-INFILTRATING

LYMPOCYTES IN PATIENTS WITH

GLIOBLASTOMA MULTIFORME CONTAIN OLIGOCLONAL POPULATIONS OF T

CELLS

W.L. Lin1, J.E.

Fincke1, A. W. Laske2, A. Kendler3,

M. Curtis4, R. Schwarting4, and C.D.

Platsoucas1*. Dept Microbiol & Immunol1,

Neurosurgery2, Dept Pathol Lab Med3

Temple Univ Sch Med, Philadelphia, PA; Dept Pathol Lab Med,

Thomas Jefferson Univ, Philadelphia, PA4

Tumor-infiltrating lymphocytes (TIL) have

been found in the majority of human and animal tumors and their

presence has been often associated with improved prognosis and

increased survival. To determine whether T cells infiltrating

brain tumors are comprised of oligoclonal populations, b -chain T-cell receptor

(TCR) transcripts from brain biopsy specimens from two patients

with glioblastoma multiforme and one with astrocytoma were

amplified by the nonpalindromic adaptor-PCR method, and the

amplified transcripts were cloned and sequenced. Sequence

analysis of b -chain TCR transcripts from one patient with

glioblastoma multiforme revealed multiple identical copies of TCR

b -chain

transcripts, suggesting the presence of oligoclonal population(s)

of T cells. These clonal expansions were confirmed using Vb -specific PCR, an

independent amplification method. b -chain TCR transcripts from the brain tumors of

the two other patients were amplified by two-sided Vb -specific PCR.

Substantial proportions of identical b -chain TCR transcripts were found in both

patients. These findings suggest that the T-cell infiltrating

these tumors are clonally expanded at the site of the tumor, in

an antigen-driven manner, in response to as yet unknown

antigen(s).