Title:Intraepithelial Attack Rather than Intratumorally Infiltration of CD8+T Lymphocytes is a Favorable Prognostic Indicator in Pancreatic Ductal Adenocarcinoma
VOLUME: 17 ISSUE: 10
Author(s):J. Zhang, Y.F. Wang, B. Wu, Z.X. Zhong, K.X. Wang, L.Q. Yang, Y.Q. Wang, Y.Q. Li, J. Gao* and Z.S. Li*
Affiliation:Department of Gastroenterology, Affiliated Hospital 1, Xi`an Jiaotong University, Xian, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, Taishan Medical University, Taian, Department of Hepatobiliary Surgery, Second Hospital of Jiaxing, Jiaxing, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, No. 411 Hospital of PLA, Shanghai, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai
Keywords:Pancreatic cancer, CD8+T lymphocytes, CD4+T lymphocytes, tumor microenvironment, prognostic
indicator, PDAC.
Abstract:Background: Tumor-infiltrating lymphocytes (TILs) are one of the major
participants in the tumor microenvironment of pancreatic ductal adenocarcinoma
(PDAC). However, the mechanism of interaction between TILs and tumors is complex
and remains unclear.
Objective: To evaluate the state of immunoreactions in PDAC tissues, and explore the
prognostic value of these markers in a large sample, to provide a new theoretical basis
for PDAC immunotherapy.
Method: Immunohistochemical staining of CD4+ and CD8+T cells was performed in a
tissue microarray (TMA) of 143 cases of PDAC. Two major variables for the spatial
distributions of CD4+T and CD8+T cells in PDAC tissues, intraepithelial attack and
intratumoral infiltration, were used to evaluate the state of immunoreactions, and the
interrelationships with the clinicopathological variables were analyzed.
Results: Our data showed that both the intraepithelial CD4+T and CD8+T attack were
less frequent than the intratumoral infiltration. CD8+T intraepithelial attack and
intratumoral infiltration were more intense than CD4+T. CD8+T intraepithelial attack was
an independent favorable prognostic factor for overall survival, correlating negatively
with vascular invasion and positively with CD4+T and CD8+T high intratumoral
infiltration. CD8+T high intratumoral infiltration without CD8+T intraepithelial attack was
a poor prognostic factor. CD8+T high intratumoral infiltration was accompanied by T
stage progression. Conclusively, in PDAC progression, imbalances of T cells occurred in
CD4+ and CD8+ immunoreactions. The CD8+T intraepithelial attack was an
independent favorable prognostic indicator, however the intraepithelial attack of CD4+T
and the both intratumoral infiltration of CD8+T and CD4+T played an ambiguous role.
Conclusion: Our data suggested that it is a potential approach to increasing the number
of intraepithelial attacking CD8+T cells for tumor immunotherapy, and exploring a new
mechanism for immunosuppression in a tumor microenvironment with high T cell
infiltration without attack.
