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Poster session 09

86P - Effect of chemotherapy-induced autophagic secretome on natural killer cell activity

Date

21 Oct 2023

Session

Poster session 09

Topics

Cancer Biology;  Tumour Immunology;  Molecular Oncology;  Cell-Based Therapy;  Immunotherapy;  Cancer Research

Tumour Site

Breast Cancer

Presenters

Ayfer Karlitepe

Citation

Annals of Oncology (2023) 34 (suppl_2): S187-S214. 10.1016/S0923-7534(23)01931-2

Authors

A. Karlitepe1, E. Celik2, T. sütlü2, T. Süzek3, M.K. Kilic Eren1

Author affiliations

  • 1 Medical Biology, Aydin Adnan Menderes University Faculty of Medicine, 09200 - Aydin/TR
  • 2 Molecular Biology And Genetics, Bogazici University, 34470 - Istanbul/TR
  • 3 Computer Engineering, Mugla Sitki Kocman University Faculty of Engineering, 48000 - Mugla/TR

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Abstract 86P

Background

Autophagy achieves a tumor-suppressing function in the initial stages of cancer by eliminating protein aggregates and damaged organelles that might promote genomic instability and lead to tumor formation. Autophagy induced by hypoxia or metabolic stress also plays an important role in the regulation of inflammatory pathways. In cancer cells, this may lead to secretion of pro- and/ or anti-inflammatory cytokines and chemokines which may help the immune escape of the tumor. However, the underlying mechanism of autophagy-mediated modulation of anti-tumor immune response is not yet fully understood. Our aim is to investigate whether chemotherapy-induced autophagy-associated secretome has the potential to modulate the NK cell-mediated anti-tumor immune responses.

Methods

Initially, western blot and immunostaining analyses were performed for autophagy markers (LC3I/II and p62) to demonstrate that Etoposide (Eto) induces autophagy in MCF-7 cells. LC/MS-MS analysis was performed to determine the content of chemotherapy-induced autophagic secretome in supernatants of autophagy-induced MCF-7 cell cultures. Finally, how the chemotherapy-induced autophagic secretome effects the capacity of DNAM1-NK-92 cells to target MCF-7 cells was determined by degranulation assays.

Results

We demonstrated Etoposide (Eto) induces autophagy in MCF-7 cells as confirmed by detection of autophagy markers including LC3I/II and p62 by WB and by immunostaining analysis. LC/MS-MS results revealed that, metabolic enzymes, tumor antigens, chaperones and metastasis-related proteins were secreted during etoposide induced autophagy which could be reduced by use of Chloroquin. When wildtype or DNAM1 overexpressing NK-92 cells were treated with autophagic secretomes, it was observed that there were differences in the capacity of targeting MCF-7 cells.

Conclusions

This study provides new insights in the field of chemo-immunotherapy by characterizing the chemotherapy-induced autophagic secretome and determining its possible effect on NK cells.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

M.K. Kilic Eren.

Funding

Adnan Menderes University Scientific Research Foundation, The Scientific and Technological Research Council of Turkey.

Disclosure

All authors have declared no conflicts of interest.

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