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
89P - Cold atmospheric plasma-activated fluids as a potential new intravesical agent for the treatment of bladder cancer
Presenter: Maria Filomena Botelho
Session: Poster session 09
90P - Discovery of CMPD1 as a tumor-specific cytotoxic microtubule inhibitor
Presenter: Mamoru Takada
Session: Poster session 09
91P - Erythroid precursor-differentiated myeloid cells promote pulmonary metastasis in hepatocellular carcinoma
Presenter: Wei-hang Zhu
Session: Poster session 09
92P - Discovery of novel AXL and MER inhibitors as potential anticancer and immune modulator drugs
Presenter: Hsing-Pang Hsieh
Session: Poster session 09
93P - Transcriptome changes of immune cells across chemotherapy of triple-negative breast cancer
Presenter: Tatiana Gerashchenko
Session: Poster session 09
509P - Spatial analysis of tumor-associated macrophages within the tumor microenvironment of primary tumors and matched brain metastases
Presenter: Markus Kleinberger
Session: Poster session 09
510P - CD47 regulates cellular and metabolic plasticity in glioblastoma
Presenter: Ruhi Polara
Session: Poster session 09
511P - Immunodisruptive conditions and glioma diagnosis: 24-year retrospective study of an under-recognized scenario
Presenter: Santiago Cabezas-Camarero
Session: Poster session 09
512P - Heterozygous germline Fanconi anemia-related gene mutations increase susceptibility to central nervous system germ cell tumors
Presenter: Guangyu Wang
Session: Poster session 09
513P - Cyclin pathway in oligodendrogliomas IDH mut and 1p/19q codeleted
Presenter: Maria Angeles Vaz Salgado
Session: Poster session 09