CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers.
We investigated intratumoral tumor-infiltrating lymphocytes (TILs), including CD4(+) and CD8(+) T cells, in non-small cell lung cancers (NSCLCs) and their relationships with clinicopathological variables and post-operative survival. Tumor specimens from 178 NSCLCs were consecutively obtained by surgery at the Hokkaido University Medical Hospital between 1976 and 1994. CD8(+) T cells, CD4(+) T cells and Ki-67/CD8(+) T cells were visualized immunohistochemically, and counted within cancer cell nests and in cancer stroma. CD8(+) T cells and CD4(+) T cells were observed at higher frequencies within cancer cell nests in moderately and poorly differentiated tumors compared with well differentiated tumors (P < 0.01), and in tumors with high Ki-67 expression compared with low Ki-67 expression (P < 0.01), that showed severe cellular atypia and a higher growth rate. Patients with higher numbers of CD8(+) T cells within cancer cell nests showed significantly shorter survival times compared to those with lower numbers of CD8(+) T cells within cancer cell nests (5-year survival rates, 47% and 60%, respectively; P = 0.03). Moreover, patients with higher labeling index of Ki-67/CD8(+) T cells showed significantly shorter survival than those with lower labeling index of Ki-67/CD8(+) T cells within cancer cell nests (5-year survival rates, 41% and 69%, respectively; P = 0.02), and the labeling index of Ki-67/CD8(+) T cells within cancer cell nests was found to be a significant and independent unfavorable prognostic factor by multivariate analysis (P = 0.01). On the other hand, higher numbers of CD4(+) T cells in cancer stroma, but not within cancer cell nests, were correlated with longer survival times in patients with NSCLC (5-year survival rates, 64% and 43%, respectively; P = 0.04). CD4(+) T cells in cancer stroma might reflect immune responses against cancer cells, while CD8(+) T cells do not appear to work as effectors in tumor tissues of NSCLC. Moreover, the higher labeling index of Ki-67/CD8(+) T cells within cancer cell nests is a strong indicator of unfavorable clinical outcome.
Wakabayashi
Osamu
O
First Department of Medicine, Hokkaido University School of Medicine, Kita-ku, Sapporo 060-8638.
Yamazaki
Koichi
K
Oizumi
Satoshi
S
Hommura
Fumihiro
F
Kinoshita
Ichiro
I
Ogura
Shigeaki
S
Dosaka-Akita
Hirotoshi
H
Nishimura
Masaharu
M
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology*; D015996:Survival Rate
D019394:Ki-67 Antigen