Effects of dexamethasone co-medication on chemo-immunotherapy treatment in murine cancer models — ASN Events
  1. Schedule
  2. Poster Session One & Burnet Oration Cocktail Function
  3. Effects of dexamethasone co-medication on chemo-immunotherapy treatment in murine cancer models

Effects of dexamethasone co-medication on chemo-immunotherapy treatment in murine cancer models (#153)

Wayne J Aston 1 , Danika E Hope 1 , Tom Casey 1 , Alistair Cook 1 , Anna K Nowak 1 2 , Richard A Lake 1 , W Joost Lesterhuis 1
  1. National Centre for Asbestos Related Diseases, University of Western Australia, Nedlands, WA, Australia
  2. Department of Medical Oncology, Sir Charles Gardiner Hospital, Perth, WA, Australia

Background:

Chemotherapy is the cornerstone of systemic treatment for metastatic cancer. Immune checkpoint blockade is now being used in several cancer types and showing durable responses but only in a small percentage of patients. Strategies to increase this response rate include combination chemo-immunotherapy, which may sensitize solid tumours to immune-mediated killing.

Chemotherapy is often accompanied by toxicities including emesis and allergic reactions. Dexamethasone, a corticosteroid, is used as an anti-emetic to reduce or prevent these, including in combination chemo-immunotherapy trials.

However, dexamethasone has immunosuppressive effects and is used in transplantation and autoimmunity. The question is whether the addition of corticosteroids may abrogate anti-tumour immune responses induced by immunotherapy.

Here we aim to investigate the degree of immunosuppression from several corticosteroids and to determine what effect they have on tumour responses to chemo-immunotherapy in murine models.

Methods

Absolute counts of T lymphocytes were obtained by flow cytometry of blood samples from patients undergoing chemotherapy plus co-medication with dexamethasone. To replicate this in mouse models, mice were treated with increasing dosages of dexamethasone and blood samples analysed on the Hemavet 950FS and with flow cytometry. Implantable tumour models were used to determine the effect of dexamethasone and other corticosteroids on therapeutic responses to chemo-immunotherapy treatment. 

Results

In patients, T cell numbers are depleted by up to 50% after treatment with dexamethasone and this was replicated in both Balb/c and C57BL/6J mice. This model is used to determine what effect dexamethasone and other corticosteroids have on immune populations in peripheral blood and the tumour. Flow cytometry and tumour growth experiments are ongoing. 

Conclusion

Treatment with dexamethasone results in a significant T cell depletion in humans and mice with cancer. A model of dexamethasone use in mice has been optimized. Updated results on flow cytometry and tumour growth will be presented at the meeting.

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