Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer

Y. Ino, R. Yamazaki-Itoh, K. Shimada, M. Iwasaki, T. Kosuge, Yae Kanai, N. Hiraoka

Research output: Contribution to journalArticle

272 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)914-923
Number of pages10
JournalBritish Journal of Cancer
Volume108
Issue number4
DOIs
Publication statusPublished - 2013 Mar 5
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Pancreatic Ductal Carcinoma
Macrophages
Survival Analysis
Neoplasms
Survival
Neutrophils
T-Lymphocytes
HLA-DR Antigens
Regulatory T-Lymphocytes
Proportional Hazards Models
Multivariate Analysis
Immunohistochemistry

Keywords

  • immune microenvironment
  • immune/inflammatory cell infiltration
  • pancreas cancer
  • prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ino, Y., Yamazaki-Itoh, R., Shimada, K., Iwasaki, M., Kosuge, T., Kanai, Y., & Hiraoka, N. (2013). Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. British Journal of Cancer, 108(4), 914-923. https://doi.org/10.1038/bjc.2013.32

Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. / Ino, Y.; Yamazaki-Itoh, R.; Shimada, K.; Iwasaki, M.; Kosuge, T.; Kanai, Yae; Hiraoka, N.

In: British Journal of Cancer, Vol. 108, No. 4, 05.03.2013, p. 914-923.

Research output: Contribution to journalArticle

Ino, Y, Yamazaki-Itoh, R, Shimada, K, Iwasaki, M, Kosuge, T, Kanai, Y & Hiraoka, N 2013, 'Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer', British Journal of Cancer, vol. 108, no. 4, pp. 914-923. https://doi.org/10.1038/bjc.2013.32
Ino, Y. ; Yamazaki-Itoh, R. ; Shimada, K. ; Iwasaki, M. ; Kosuge, T. ; Kanai, Yae ; Hiraoka, N. / Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. In: British Journal of Cancer. 2013 ; Vol. 108, No. 4. pp. 914-923.
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abstract = "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.",
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AU - Ino, Y.

AU - Yamazaki-Itoh, R.

AU - Shimada, K.

AU - Iwasaki, M.

AU - Kosuge, T.

AU - Kanai, Yae

AU - Hiraoka, N.

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.

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KW - immune/inflammatory cell infiltration

KW - pancreas cancer

KW - prognosis

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