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
1851 - Nivolumab-induced and radiation recall pneumonitis in patients with non-small cell lung cancer: a multicenter real world analysis of 669 patients
Presenter: Nobuaki Mamesaya
Session: Poster Display session 1
Resources:
Abstract
851 - Retrospective analysis of immunotherapy prognostic scores in advanced NSCLC at Nottingham University Hospitals (UK)
Presenter: Cristina Lopez Escola
Session: Poster Display session 1
Resources:
Abstract
3639 - Applicability of lung immune prognostic index (LIPI) to predict efficacy of first-line pembrolizumab in advanced non-small-cell lung cancer (NSCLC)
Presenter: Xabier Mielgo Rubio
Session: Poster Display session 1
Resources:
Abstract
2950 - Delayed Onset Immune Related Adverse Effects (IRAEs) of Pembrolizumab in Non-Small Cell Lung Cancer
Presenter: Haixi Yan
Session: Poster Display session 1
Resources:
Abstract
3659 - Clinical implication of multiplex IHC and serologic biomarkers on Hyperprogression in NSCLC patients receiving Immune checkpoint blockers in real world.
Presenter: Joori Kim
Session: Poster Display session 1
Resources:
Abstract
4882 - Local ablative treatment and treatment beyond progression for oligo-progression in stage IV non-small cell lung cancer after tumor response to anti-PD1 treatment
Presenter: Florian Guisier
Session: Poster Display session 1
Resources:
Abstract
1358 - Atezolizumab in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs)
Presenter: Francis Mogollon-Duffo
Session: Poster Display session 1
Resources:
Abstract
2170 - Prognostic Impact of Metastatic Sites for Pembrolizumab Efficacy as First-line therapy in Patients with PD-L1 tumor proportion score (TPS) ≥ 50% Advanced Non–Small Cell Lung Cancer: A Retrospective Multicenter Study
Presenter: Hayato Kawachi
Session: Poster Display session 1
Resources:
Abstract
3051 - Impact of visceral fat area as independent predictive factor in patients with advanced non-small cell lung cancer treated with nivolumab
Presenter: Yuki Sato
Session: Poster Display session 1
Resources:
Abstract
3409 - Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
Presenter: Toshihiko Iuchi
Session: Poster Display session 1
Resources:
Abstract