Abstract 5817
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3690 - PD-L1 expression in resected undifferentiated pleomorphic sarcoma and its clinical implications
Presenter: Kyoungmin Lee
Session: Poster Display session 1
Resources:
Abstract
2013 - PD-L1 expression as a potential therapeutic target and prognostic biomarker in well-differentiated and dedifferentiated liposarcoma.
Presenter: Heejung Chae
Session: Poster Display session 1
Resources:
Abstract
5021 - Soft tissue sarcomas express a distinct mRNA immune profile
Presenter: Viktor Grünwald
Session: Poster Display session 1
Resources:
Abstract
3029 - The molecular landscape of fusion genes in endometrial stromal sarcomas include three nosological entities with different natural history
Presenter: Mehdi Brahmi
Session: Poster Display session 1
Resources:
Abstract
3914 - Clinical validation of a novel assay for the detection of diagnostic alterations in sarcomas
Presenter: Lauren Mc Connell
Session: Poster Display session 1
Resources:
Abstract
1912 - A prospective correlative trial of personalized patient-derived xenograft (PDX) as avatars for drug therapy in patients with metastatic or recurrent soft tissue sarcomas (STS).
Presenter: Kanan Alshammari
Session: Poster Display session 1
Resources:
Abstract
5097 - Fusion of immortalized myoblasts induces genomic instability that drives tumor development and progression.
Presenter: Candice Merle
Session: Poster Display session 1
Resources:
Abstract
1383 - let-7a suppress Ewing sarcoma CSCs' malignant phenotype through forms a positive feedback regulation loop with lin28 via STAT3
Presenter: Xu Jiang
Session: Poster Display session 1
Resources:
Abstract
3386 - Myoepithelial Tumors of Soft Tissues and Extraskeletal Myxoid Chondrosarcomas feature a distinct transcriptional pattern
Presenter: Dominga Racanelli
Session: Poster Display session 1
Resources:
Abstract
1844 - In Vivo Efficacy and Enhanced Tumor Accumulation of Liposomal Vinorelbine (TLC178) in Human Sarcoma Xenograft Mice Model
Presenter: Wan-ni Yu
Session: Poster Display session 1
Resources:
Abstract