Abstract 3155: A study on characteristics of stromal fibrosis and tumor-infiltrating lymphocytes in peritoneal metastasis of colorectal cancer
Authors: Wang En , Shibutani Masatsune , Nagahara Hisashi , Fukuoka Tatsunari , Iseki Yasuhito , Okazaki Yuki , Kashiwagi Shinichiro , Tanaka Hiroaki , Maeda Kiyoshi , Hirakawa Kosei , Ohira Masaichi 
Published: July 2021

Abstract
[Background] Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the anti-tumor immune status and correlate with the prognosis and therapeutic outcomes. However, recent investigations have demonstrated that the level of TIL infiltration varies depending on the metastatic organ, and intratumoral fibrosis is important as a factor affecting the infiltration of TILs. The present study investigated the organ specificities of TIL infiltration and intratumoral fibrosis in primary colorectal cancer and distant metastases, including peritoneal metastases, as well as the relationship between the distribution of TILs and intratumoral fibrosis.
[Methods] Patients who underwent resection of primary tumors or distant metastases for colorectal cancer with distant metastases from 1994 to 2019, including 67 cases of peritoneal metastases, 39 cases of primary tumors with simultaneous resection of peritoneal metastases, 138 cases of liver metastases, and 25 cases of lung metastases, were enrolled. We evaluated the TIL infiltration by immunohistochemical staining with anti-CD3 and CD8 antibodies and intratumoral fibrosis by immunohistochemical staining with anti-α-SMA antibody against cancer-associated fibroblasts (CAFs) and Masson's trichrome staining against collagen fibers. The software program "ImageJ" was used to evaluate fibrosis, by which the intensity and range of fibrosis were determined, and the density of TILs in the dense and sparse areas of fibrosis was calculated.
[Results] The level of CD3+TIL infiltration in peritoneal metastases was significantly lower than that in primary tumors, liver metastases, and lung metastases, and the level of CD8+TIL infiltration in peritoneal metastases was significantly lower than that in liver metastases and lung metastases (median CD3+TILs: peritoneal metastases 9.0 vs. primary tumors 15.2 vs. liver metastases 13.1 vs. lung metastases 20.0; median CD8+TILs: peritoneal metastases 1.8 vs. primary tumors 3.4 vs. liver metastases 5.4 vs. Lung metastases 8.4;/x400HPF). The area ratio of α-SMA+CAF and collagen fibers in peritoneal dissemination was significantly higher than that of primary lesions, liver metastases, and lung metastases (median α-SMA+CAF: peritoneal metastasis 23.53% vs. primary lesion 18.55%. vs. liver metastases 11.25% vs. lung metastases 12.78%; median collagen fibers: peritoneal metastases 15.64% vs. primary lesions 11.49% vs. liver metastases 8.13% vs. lung metastases 9.18%). Furthermore, the density of TILs in the high-fibrosis area was significantly lower than that in the low-fibrosis area.
[Conclusion] Lymphocytes have difficulty infiltrating areas of high fibrosis, and the infiltration of T lymphocytes into tumors is prevented in peritoneal metastases of colorectal cancer due to the high intratumoral fibrosis, which may lead to treatment resistance and a poor prognosis.
Citation Format: En Wang, Masatsune Shibutani, Hisashi Nagahara, Tatsunari Fukuoka, Yasuhito Iseki, Yuki Okazaki, Shinichiro Kashiwagi, Hiroaki Tanaka, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira. A study on characteristics of stromal fibrosis and tumor-infiltrating lymphocytes in peritoneal metastasis of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3155.