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
1842 - Immunological impact of surgery in NSCLC patients
Presenter: Akitoshi Yanagihara
Session: Poster Display session 1
Resources:
Abstract
4124 - The prognostic value of selected immunological panel in predicting the prognosis of early-stage resectable non-small cell lung cancer
Presenter: Sha Zhao
Session: Poster Display session 1
Resources:
Abstract
4468 - Genomic Heterogeneity and Clonality Analysis of Multiple synchronous lung cancers (MSLCs)
Presenter: Fachen Zhou
Session: Poster Display session 1
Resources:
Abstract
5547 - Analysis of immunosuppressive factors produced by tumorspheres in NSCLC. Prognostic value of Galectin-3 in adenocarcinoma
Presenter: Susana Torres Martinez
Session: Poster Display session 1
Resources:
Abstract
1658 - Frequency of epidermal growth factor receptor (EGFR) mutations in stage IB–IIIA EGFR mutation positive non-small-cell lung cancer (NSCLC) after complete tumour resection
Presenter: Masahiro Tsuboi
Session: Poster Display session 1
Resources:
Abstract
1535 - EGFR mutation is not a prognostic factor in completely resected lymph node–negative pulmonary adenocarcinoma (LNNPA)
Presenter: Nussara Leeladejkul
Session: Poster Display session 1
Resources:
Abstract
3262 - Prognostic significance of elements of the adaptive immunity in the microenvironment of early-stage non small cell lung cancer
Presenter: Aliki Liakea
Session: Poster Display session 1
Resources:
Abstract
4643 - Combined immunoscore for prognostic stratification of early stage NSCLC patients
Presenter: Giulia Pasello
Session: Poster Display session 1
Resources:
Abstract
4819 - Radiation-induced lung injury and misdiagnosis rate after SBRT
Presenter: Xiaolong Fu
Session: Poster Display session 1
Resources:
Abstract
681 - Significance of the red blood cell distribution width in resected pathological stage I non-small cell lung cancer
Presenter: Gouji Toyokawa
Session: Poster Display session 1
Resources:
Abstract