Research Papers:

Verification of the methodology for evaluating tumor-infiltrating lymphocytes in colorectal cancer

Shinji Matsutani, Masatsune Shibutani _, Kiyoshi Maeda, Hisashi Nagahara, Tatsunari Fukuoka, Yasuhito Iseki, Kosei Hirakawa and Masaichi Ohira

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Oncotarget. 2018; 9:15180-15197. https://doi.org/10.18632/oncotarget.24612

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Shinji Matsutani1, Masatsune Shibutani1, Kiyoshi Maeda1, Hisashi Nagahara1, Tatsunari Fukuoka1, Yasuhito Iseki1, Kosei Hirakawa1 and Masaichi Ohira1

1Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan

Correspondence to:

Masatsune Shibutani, email: [email protected]

Keywords: tumor-infiltrating lymphocytes; TILs; prognostic marker; colorectal cancer; methodology

Received: May 23, 2017     Accepted: February 21, 2018     Epub: March 08, 2018     Published: March 16, 2018


Background: The density of tumor-infiltrating lymphocytes (TILs) have been reported to reflect antitumor immune response and correlate with prognosis in malignancy. However, the methodology for evaluating the density of TILs by an immunohistochemical analysis differs among reports. The aim of this study was to verify the methodology for evaluating the density of TILs by immunohistochemical analysis and thereby identify the optimum methodology in clinical setting.

Methods: Three-hundred-thirteen patients who underwent curative operation for stage II/III colorectal cancer were enrolled. We retrospectively examined the density of TILs using immunohistochemical staining according to each method as follows: 1) subset of lymphocytes (i.e. CD4+/CD8+), 2) selected fields (i.e. at random or focusing on hot spots), 3) location in low-power field (i.e. the invasive margin [TILsIM] or the center of the tumor [TILsCT] or the surface of the tumor [TILsST]), and 4) location in high-power field (i.e. in tumor stroma [sTILs] or intra-tumor cells [iTILs] or total TILs [tTILs: sTILs+iTILs]). We then assessed the prognostic value of the density of TILsIM evaluated as described above. We also evaluated the correlation between the density of TILsIM and that of TILsCT/TILsST.

Results: Only the densities of CD8+sTILsIM and CD8+tTILsIM evaluated in randomly selected fields were significantly associated with the survival. Furthermore, the density of CD8+TILsIM was significantly associated with that of CD8+TILsCT and CD8+TILsST.

Conclusions: We concluded that best and easiest way to evaluate the density of TILs in the clinical setting may be to assess the density of CD8+tTILsIM in randomly selected fields.

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