Abstract 2316
Background
Neoadjuvant chemotherapy (NACT) is the treatment option for locally advanced breast cancer (BC). However, more than half of the patients have no response. Thus, there is an urgent need to find biomarkers of NACT response and personalized therapies for non-responders. Recently, we described a biomarker of NACT response, assessed both in biopsy and blood - HLA-DR expressing cytotoxic T cells (CTLs) with a sensitivity and specificity of 94.12% and 100%, respectively. HLA-DR is associated with CTLs’ cytotoxicity, and it was only observed in NACT-responders, suggesting that functional CTLs are required in the tumor for NACT success. Now, we are validating these results in an independent cohort. Simultaneously, we are establishing 3D spheroid co-culture platforms to tackle new therapeutic options for NACT non-responders.
Methods
MCF7 BC cell line was used to spontaneously form a spheroid in agarose coated plates. Peripheral blood mononuclear cells (PBMCs) from NACT-responders or non-responders were added after spheroid formation and they were able to infiltrate the structure. Doxorubicin (doxo), anti-PD-1 and anti-PD-L1 were added in different combinations.
Results
The validation of HLA-DR level in CTLs to predict NACT response has been in agreement with the first cohort. Regarding the BC spheroids, doxo alone or in combination with NACT non-responders PBMCs (low HLA-DR in CTLs) did not affect them. However, when PBMCs from NACT responders (high HLA-DR in CTLs) were added in combination with doxo, the viability and proliferation of MCF7 cells reduced significantly. Notably, when PBMCs from NACT non-responders were stimulated ex vivo, to increase CTLs’ HLA-DR level and IFN-γ production (p = 0.002), MCF7 cells viability decreased (p = 0.0007). Considering that in biopsies of non-responders, the low HLA-DR level in CTLs was negatively correlated with the expression of tumor PD-L1, we are also exploring this platform to inhibit the PD-1/PD-L1 axis in order to stimulate the PBMCs and decrease BC cells viability.
Conclusions
Besides determining if BC patients will respond to NACT, by analysing HLA-DR levels in CTLs, we will now be able to define the best therapy to NACT non-responders, hopefully improving the BC treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Fundação para a Ciência e Tecnologia (FCT) - PD/BD/114023/2015 and PTDC/BBB-BMD/4497/2014. Liga Portuguesa Contra o Cancro - LPCC-NRS/Terry Fox 2019/2020.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2888 - Development and validation a nomogram based on pathological microscopic features to predict survival in nasopharyngeal carcinoma and guide treatment decision
Presenter: Kuiyuan Liu
Session: Poster Display session 3
Resources:
Abstract
3607 - Deep learning in nasopharyngeal carcinoma: a retrospective cohort study of 3D convolutional neural networks on magnetic resonance imaging
Presenter: Meng Yun Qiang
Session: Poster Display session 3
Resources:
Abstract
5848 - Combined androgen blockade in patients with advanced androgen receptor–positive salivary gland carcinoma: Exploratory biomarker analyses
Presenter: Chihiro Fushimi
Session: Poster Display session 3
Resources:
Abstract
4484 - Classification of esthesioneuroblastoma (ENB) based on chromosome (chr) arm gain and loss (CNA) in the setting of a hypomutated genomic landscape
Presenter: Russell Madison
Session: Poster Display session 3
Resources:
Abstract
5753 - Trastuzumab plus docetaxel in patients with advanced HER2–positive salivary duct carcinoma: Exploratory biomarker analyses
Presenter: Hideaki Takahashi
Session: Poster Display session 3
Resources:
Abstract
3373 - Development and characterization of salivary gland cancer organoid cultures
Presenter: Wim Boxtel
Session: Poster Display session 3
Resources:
Abstract
3118 - A parent-of-origin effect of the RB1 mutations in retinoblastoma with low penetrance and variable expressivity
Presenter: Ekaterina Alekseeva
Session: Poster Display session 3
Resources:
Abstract
4512 - The humanistic burden reported by patients diagnosed with Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) in Europe
Presenter: Prianka Singh
Session: Poster Display session 3
Resources:
Abstract
3961 - Concurrent Chemotherapy and External Radiation Therapy: An Open Label Non-Inferiority Phase III Randomized Controlled Trial of Weekly versus Three Weekly Cisplatin and Radical Radiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: CONCERT trial
Presenter: ATUL SHARMA
Session: Poster Display session 3
Resources:
Abstract
3973 - A randomized phase II study on the OPTimization of IMmunotherapy in squamous carcinoma of the head and neck (SCCHN) – OPTIM (AIO-KHT-0117)
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract