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Regular and Young Investigator Award Abstracts
Immune Cell Types and Biology
1040 Immune profiling of aged mice bearing glioblastoma
  1. Sarah Cook1,
  2. Kelly Hotchkiss1,
  3. Eliese Moelker1,
  4. Eugene Cho1,
  5. Aditya Mohan1,
  6. John Sampson2 and
  7. Mustafa Khasraw3
  1. 1Duke University, Durham, NC, USA
  2. 2Duke University Medical Center, Durham, NC, USA
  3. 3Duke Cancer Institute, Durham, NC, USA

  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.

Abstract

Background Glioblastoma (GBM) remains uniformly fatal with a median overall survival (OS) of <21 months. There is a disconnect between multiple promising preclinical findings and disappointing clinical trial results. A contributing factor could be that preclinical studies rely on young 6–8 week old mice while the median patient age at diagnosis of GBM is 64 years. Previous preclinical studies have shown that aged GBM bearing mice have reduced OS in comparison to younger mice, and that the response to immunotherapy in aged tumor bearing mice is inferior. To further understand this issue we have conducted immune profiling in the brain and periphery of young and aged mice

Methods Young (6–8 week) or aged (11 month+) C57BL/6 mice were implanted intracranially with CT2A tumors. The immune profiles of the local immune environment (brain) and peripheral immune cells (spleen and blood) of either naïve or tumor-bearing mice was determined by flow cytometry on day 14 post tumor implantation.

Results In this study, we observed higher overall brain weights of older mice compared to condition matched young mice. Within the naïve groups, the proportions of immune cells were significantly lower in the brains older mice: CD8+ T cells, p<0.008; B cells, p<0.04; and microglia, p<0.02. The presence of a brain tumor counteracted the effects of age on brain immune composition of CD8+ T cells, B cells and microglia but greatly reduced the eosinophil population (p<0.008) in aged mice. This modulation of eosinophils is also reflected peripherally, with fewer eosinophils in the spleen of aged tumor bearing mice (p<0.008).

Conclusions We observed differences in immune profiles of the brain and periphery of the tumor-bearing aged mice in comparison to tumor-bearing young mice. Of particular note are a reduction in eosinophils in aged mice, which is known to result in worse overall survival in GBM. These differences may impact the effectiveness of immunotherapy in aged populations. Subsequent studies will include the functional activity of immune cells from both young and aged tumor bearing mice and interrogating changes in specimens from our immunotherapy clinical trials conducted in older and younger patients with GBM

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

http://dx.doi.org/10.1136/jitc-2023-SITC2023.1040

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