Evidence for existence of oligoclonal tumor-infiltrating lymphocytes and predominant production of T helper 1/T cytotoxic 1 type cytokines in gastric and colorectal tumors.
Tumor-infiltrating lymphocytes (TIL) play a central role in cellular immunity against tumor. We have revealed the characteristics of TILs in terms of T-cell receptor (TCR) repertoire, T-cell clonality, and cytokine production. TCR repertoire analyses and CDR3 size spectratyping were performed using peripheral blood mononuclear cells (PBMCs) and tissue specimens of gastric or colorectal cancers surgically resected from 11 patients. The cytokine expression was measured by real-time quantitative polymerase chain reaction. TCR repertoires were similar among multiple tissue specimens from different sites of the same tumor. Similar peak patterns of CDR3 size spectratyping were observed among these tumor specimens, but not in normal tissues or PBMCs. In addition, identical peaks were detected in multiple specimens of the same tumor. The ratio of the levels of IFN-gamma to that of IL-4 is significantly higher for tumor lesions compared with PBMCs. These results suggested that a limited number of TILs locally expand in response to tumor antigens exiting within gastric or colorectal cancers and local predominant production of the T helper 1/T cytotoxic 1 type cytokine may affect the anti-tumor immune response of TILs.
Matsutani
Takaji
T
Division of Immunology and Embryology, Department of Cell Biology, Tohoku University School of Medicine, Sendai 980-8575, Japan. matsu@immem.med.tohoku.ac.jp
Shiiba
Ken-Ichi
K
Yoshioka
Takeshi
T
Tsuruta
Yuji
Y
Suzuki
Ryuji
R
Ochi
Takahiro
T
Itoh
Tsunetoshi
T
Musha
Hiroaki
H
Mizoi
Takayuki
T
Sasaki
Iwao
I
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D022801:Complementarity Determining Regions / Q000235:genetics; D016207:Cytokines / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D016133:Polymerase Chain Reaction; D012004:Rectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology
D022801:Complementarity Determining Regions; D016207:Cytokines; D010446:Peptide Fragments; D015847:Interleukin-4; D007371:Interferon-gamma