Abstract 24P
Background
Chemotherapy is the mainstay of systemic treatment for patients with triple-negative breast cancer (TNBC) due to the lack of targets for targeted therapy (HER2/neu; ER; PR). Components of the immune system are known to be involved in the response to chemotherapeutic treatment. Here we aimed to study the dynamics of changes in immune cell composition during neoadjuvant chemotherapy (NACT).
Methods
The immune cells were purified from peripheral blood and biopsy samples of 5 TNBC patients before NACT and 21st days of first course of NACT (AC regimen). Total cell concentration and viability (Calcein/DRAQ7) were assessed by flow cytometry (Cytoflex, Beckman Coulter). Single cells were sequenced on a Genolab M platform (GeneMind Biosciences) using 10x Genomics technology for fixed multiplexed samples. Data were analyzed using Seurat and SingleR.
Results
Sequencing revealed a variety of immune cell populations including: B cells, DC cells, NK cells, CD4+, CD8+ and T regulatory lymphocytes, classical and non-classical monocytes, granulocytes and others. In the blood, the pool of classical monocytes and NK cells were depleted up to day 21 after the first NACT cycle, while naive CD4+, CD8+ T cells and end effector CD8+ T cells, were increased by day 21. In the populations of monocytes and NK cells overexpression of RGS2, ANXA1, FGL2, MX1, IFI6 genes were observed, involved in induction apoptosis. CD8+T-cells, as well as Th-1 and Th-2 CD4+ T-cells were characterized by increased expression of NFKBIA, JUN, FOS, involved in T cell differentiation. In the tumor microenvironment, depletion of CD4+ T cells, CD8+ T cells and memory B cells and an increase in T-regulatory cells and plasma cells were observed. DUSP4, LCK, CXCR4, LTB, TNFRSF18, IL2RB and PTPN7 genes were overexpressed and involved in the regulation of cytokine secretion and inhibition of TCR signaling in CD4+ and CD8+ T cells; chemotaxis-mediated inflammation in memory B cells; T cells differentiation, and induction of invasion/migration of tumor cells in T-regulatory cells and plasma cells.
Conclusions
The first cycle of NACT induced renewal of the immune cells’ composition in the blood and tumor microenvironment skewing towards to immune disfunction.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation.
Funding
Russian Science Foundation (grant #22-75-10128).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
46P - Effect of coadministration of antioxidant chlorophyllin with docetaxel on invasion and metastasis in triple-negative breast cancer in vivo/in vitro
Presenter: Ayse Burus
Session: Poster session 09
47P - An ozone delivery system by cisplatin prodrug self-assembling micelles combining microwave to sensitizing immune checkpoint inhibitor in triple-negative breast cancer
Presenter: Dan Zheng
Session: Poster session 09
48P - Non-steroid anti-inflammatory treatment enhances the efficacy of modulated electro hyperthermia on triple-negative breast cancer and melanoma cancer models in vivo
Presenter: Nino Giunashvili
Session: Poster session 09
49P - Circulating miRNA signatures to predict recurrence in patients with pathological complete response of triple-negative breast cancer
Presenter: Ana Julia de Freitas
Session: Poster session 09
50P - Application and mechanism of tarloxotinib in HER2-positive breast cancer
Presenter: Xinyi Shao
Session: Poster session 09
51P - Nanoengineered sonosensitive platelets for synergistically augmented sonodynamic breast tumour therapy by glutamine deprivation and cascading thrombosis
Presenter: Liqiang Zhou
Session: Poster session 09
53P - Treatment of cancer cells based on circulating tumor cell’s expression profile using off-label drugs
Presenter: Panagiotis Apostolou
Session: Poster session 09
54P - Enhanced oxidative phosphorylation of metastasis-initiating cells facilitates esophageal tumor cell seeding in lymph nodes
Presenter: Shanshan Li
Session: Poster session 09
55P - Transcriptional profiles of engineered T cells stimulated with different receptor structures and co-stimulatory domains
Presenter: Ungue Shin
Session: Poster session 09
56P - SLC34A2-ROS1 L2026M+G2032R confers resistance to ROS1 tyrosine kinase inhibitors in Ba/F3 cells through a reduced ATP binding pocket volume
Presenter: Christa Dijkhuizen
Session: Poster session 09