The predictive value and role of stromal tumor-infiltrating lymphocytes in pancreatic ductal adenocarcinoma (PDAC)

ABSTRACT

Recently, increasing evidence has indicated that the presence of tumor infiltrating immune cells has shown predictive significance for many solid tumors. Present study was performed to evaluate the predictive value of stromal tumor-infiltrating lymphocytes (TILs) for the presence of liver metastasis and overall survival in PDAC (pancreatic ductal adenocarcinoma) patients after complete resection and to explore the potential role of lymphocytes in PDAC. A total of 155 resectable patients with PDAC were enrolled in our study. Stromal TIL density was investigated in hematoxylin and eosin-stained sections of surgical specimens and scored. The effect and possible mechanism of lymphocytes on cancer cells was evaluated using co-culture techniques and ELISA test. Stromal TIL negative status (HR = 2.80, 95% CI 1.75-4.48, P < 0.01) was not only an independent predictor of worse OS (HR = 2.7, 95% CI 1.80-4.06, P = <0.01) but also a significant independent predictor of liver metastasis. Higher CEA (P = 0.01) or CA19-9 (P = 0.01) levels were associated with low stromal TIL density. Stromal TIL negative patients appeared to develop tumors with a higher CEA (P = 0.01), larger diameter (P = 0.05) and advanced stage (P = 0.02). The co-culture experiment suggests that lymphocytes can inhibit pancreatic cancer cell proliferation. Further ELISA and cell culture test indicate that lymphocytes may cause pancreatic cancer cells apoptosis through TNF-alpha secretion. Our data suggest a potential favorable role of stromal TILs in predicting liver metastasis and overall survival of patients with PDAC after complete resection. Lymphocytes may inhibit the growth of PDAC through TNF-alpha secretion, which suggest a potential therapeutic approach against PDAC.

KEYWORDS:

• tumor-infiltrating lymphocytes
• pancreatic ductal adenocarcinoma
• prognosis, TNF-alpha

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Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Authors contributions

Dr. Xiu Dianrong and Tao Lianyuan conceived and designed this study; Tao Lianyuan performed the HE, IHC and cell culture; Tao Lianyuan, Xiu Dianrong, Yuan Chunhui, Ma Zhaolai and Jian Bing performed the statistical analysis and interpreted the data; Xiu Dianrong and Tao Lianyuan wrote the manuscript. All authors reviewed and accepted the final manuscript for submission.

Additional information

Funding

This study was supported by a grant from the National Natural Science Foundation of China (No. 81672862) and the Capital Characteristic Clinical Application Research and Achievement Promotion Project (No. Z171100001017121).