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Poster Display session 1

5817 - Functional analysis of tumor infiltrating lymphocytes in triple negative breast cancer focusing on granzyme B


28 Sep 2019


Poster Display session 1


Basic Science

Tumour Site

Breast Cancer


Hitomi Kawaji


Annals of Oncology (2019) 30 (suppl_5): v1-v24. 10.1093/annonc/mdz238


H. Kawaji1, M. Kubo2, Y. Motoyama1, A. Shimazaki1, S. Hayashi1, K. Kurata1, M. Yamada2, K. Kaneshiro1, M. Kai2, M. Nakamura2

Author affiliations

  • 1 Surgery And Oncology, Kyushu University - Graduate School of Medical Sciences - Faculty of medical Sciences, 812-8582 - Fukuoka/JP
  • 2 Surgery And Oncology, Kyushu University Hospital, 812-8582 - Fukuoka/JP


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Abstract 5817


Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes in breast cancer and has a worse prognosis than others. Tumor infiltrating lymphocytes (TIL) are considered to be a prognostic factor in TNBC. Cytotoxic T cells (CTL) produce cytokines and cytotoxic substances such as perforin and granzyme B, and attack target cells. We have previously shown that combination of PD-L1 expression and TIL is useful as a functional indicator of tumor immune activation. Granzyme B released from CTL induces apoptosis by passing through pores formed by perforin on the cell membrane of target cells. We focused on the cytotoxic substance granzyme B and explored functional of TIL.


This study included 228 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at Kyushu University Hospital (Japan), between January 2004 and December 2014. We retrospectively analyzed granzyme B, CD8, PD-L1 expression assessed by immunohistochemistry and TIL in 228 TNBCs. Granzyme B was evaluated in TIL, ≥ 3% was defined as high expression, and < 3% as low. We also explored the correlation between immunologic features on tumors and immune cells and the clinicopathological characteristics of the tumors, their response to chemotherapy and clinical outcome.


Among the 228 tumors, granzyme B expression was classified as high in 106 (46.5%), low in 122 (53.5%). Granzyme B-high is correlated with high levels of TIL (p = 0.004), CD8 expression of T cell (p = 0.016) and PD-L1 of tumor cells (p<.0001). In the TIL-high and granzyme B-high group, it is considered that the anti-tumor immune system is activated, and it tend to be the most favorable prognosis. On the other hand, in the TIL-high and granzyme B-low group, despite lymphocyte migration, it is presumed that they do not recognize the antigen, that is, they are in a state of immune tolerance and thus have a poor prognosis. In the group with granzyme B-high, the patients treated with anthracycline as adjuvant chemotherapy significantly improved their prognosis (p = 0.043). The high expression of granzyme B may be a predictor of postoperative chemotherapy.


Granzyme B is an important substance of cytotoxic pathway and has been possible to be an indicator of TIL activation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Masafumi Nakamura.


Has not received any funding.


All authors have declared no conflicts of interest.

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