CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma

Akira Fukunaga, Masaki Miyamoto, Yasushi Cho, Soichi Murakami, You Kawarada, Taro Oshikiri, Kentaro Kato, Takanori Kurokawa, Masato Suzuoki, Yoshihiro Nakakubo, Kei Hiraoka, Tomoo Itoh, Toshiaki Morikawa, Shunichi Okushiba, Satoshi Kondo, Hiroyuki Katoh
Pancreas 2004, 28 (1): e26-31

OBJECTIVE: Recent studies have demonstrated the importance of tumor immunity for a cancer patient's prognosis. In some types of cancer, it has been shown through immunohistochemical analysis that the existence of CD8+ tumor-infiltrating lymphocytes (TILs) is a crucial factor in determining prognosis. In an experimental model, CD4+ lymphocytes together with CD8+ lymphocytes contributed significantly to tumor immunity.

METHODS: Specimens were taken from 80 surgically resected pancreatic adenocarcinomas between 1992 and 1999. Immunohistochemical staining of CD4, CD8, and S100 protein was performed, and the levels of these proteins were determined by microscopic analysis. The percentages of patients in the CD4(+) and CD8(+) groups were 59% (47/80) and 25% (16/80), respectively. When separated into 4 groups, CD4/8(+/+), CD4/8(+/-), CD4/8(-/+) and CD4/8(-/-), the overall survival rate was significantly higher in CD4/8(+/+) patients (13 cases) compared with those in all other groups combined (67 cases; P = 0.0098). CD4/8(+/+) status was negatively correlated with tumor depth and TNM stage. Multivariate analyses showed that CD4/8(+/+) status was an independent favorable prognostic factor. The number of tumor-infiltrating S100 protein positive cells was also significantly higher in the CD4/8(+/+) group than in others (P = 0.0084).

CONCLUSIONS: In pancreatic adenocarcinoma, the presence of CD4+ TILs together with CD8+ TILs serves as a good indicator of the patient's outcome after surgical treatment.

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