TY - JOUR
T1 - Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer
AU - Ino, Y.
AU - Yamazaki-Itoh, R.
AU - Shimada, K.
AU - Iwasaki, M.
AU - Kosuge, T.
AU - Kanai, Y.
AU - Hiraoka, N.
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Third Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan (NH), Princess Takamatsu Cancer Research Fund (10-24216) (NH), Pancreas Research Foundation of Japan (NH), and the National Cancer Center Research and Development Fund (NH). We thank Drs Kazufumi Honda, Tomohiro Sakuma, and Kimio Yoshimura for kindly advising statistical analyses and Drs Hidenori Ojima, Minoru Esaki, Satoshi Nara, and Yoji Kishi for useful discussion.
PY - 2013/3/5
Y1 - 2013/3/5
N2 - Background:The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact.Methods:Using immunohistochemistry, we examined tumour-infiltrating CD68 + pan-macrophages, HLA-DR + CD68 + M1 macrophages (M1), CD163 + or CD204 + M2 macrophages (M2), CD66b + neutrophils (Neu), CD4 + T cells (CD4 + T), CD8 + T cells (CD8 + T), and FOXP3 + CD4 + regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan-Meier method and Cox proportional hazards model.Results:Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4 + T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4 + T, CD8 + T, or the ratio of M1 to pan-macrophages (%M1) were significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4 + T high /CD8 + T high /%Treg low and tumour-infiltrating %M1 high /M2 low. Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio.Conclusion:Tumour-infiltrating CD4 + T high /CD8 + T high /%Treg low and %M1 high /M2 low are independent prognosticators useful for evaluating the immune microenvironment of PDC.
AB - Background:The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact.Methods:Using immunohistochemistry, we examined tumour-infiltrating CD68 + pan-macrophages, HLA-DR + CD68 + M1 macrophages (M1), CD163 + or CD204 + M2 macrophages (M2), CD66b + neutrophils (Neu), CD4 + T cells (CD4 + T), CD8 + T cells (CD8 + T), and FOXP3 + CD4 + regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan-Meier method and Cox proportional hazards model.Results:Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4 + T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4 + T, CD8 + T, or the ratio of M1 to pan-macrophages (%M1) were significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4 + T high /CD8 + T high /%Treg low and tumour-infiltrating %M1 high /M2 low. Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio.Conclusion:Tumour-infiltrating CD4 + T high /CD8 + T high /%Treg low and %M1 high /M2 low are independent prognosticators useful for evaluating the immune microenvironment of PDC.
KW - immune microenvironment
KW - immune/inflammatory cell infiltration
KW - pancreas cancer
KW - prognosis
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U2 - 10.1038/bjc.2013.32
DO - 10.1038/bjc.2013.32
M3 - Article
C2 - 23385730
AN - SCOPUS:84875228204
SN - 0007-0920
VL - 108
SP - 914
EP - 923
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 4
ER -
