PreprintReviewVersion 2Preserved in Portico This version is not peer-reviewed
Obesity Is Associated With Immunometabolic Changes in Adipose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies
Version 1
: Received: 24 February 2023 / Approved: 28 February 2023 / Online: 28 February 2023 (02:26:46 CET)
Version 2
: Received: 23 March 2023 / Approved: 24 March 2023 / Online: 24 March 2023 (02:09:14 CET)
Savva, C.; Copson, E.; Johnson, P.W.M.; Cutress, R.I.; Beers, S.A. Obesity is Associated with Immunometabolic Changes in Adipose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies. Cancers2023, 15, 2440.
Savva, C.; Copson, E.; Johnson, P.W.M.; Cutress, R.I.; Beers, S.A. Obesity is Associated with Immunometabolic Changes in Adipose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies. Cancers 2023, 15, 2440.
Savva, C.; Copson, E.; Johnson, P.W.M.; Cutress, R.I.; Beers, S.A. Obesity is Associated with Immunometabolic Changes in Adipose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies. Cancers2023, 15, 2440.
Savva, C.; Copson, E.; Johnson, P.W.M.; Cutress, R.I.; Beers, S.A. Obesity is Associated with Immunometabolic Changes in Adipose Tissue That May Drive Treatment Resistance in Breast Cancer: Immune-Metabolic Reprogramming and Novel Therapeutic Strategies. Cancers 2023, 15, 2440.
Abstract
White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue that’s primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression. The role of adiposity and systemic inflammation in immune responses and resistance to anti-cancer treatment in breast cancer (BC) patients is still not clear. This review aims to evaluate the emerging evidence on the crosstalk between adiposity and the immune-tumour microenvironment in BC, its progression and treatment resistance. Adiposity, and by extension subclinical inflammation, are associated with metabolic dysfunction and changes in the immune-tumour microenvironment in BC. In oestrogen receptor positive (ER+) breast tumours, it is proposed that these changes are mediated via a paracrine interaction between macrophages and preadipocytes leading to elevated aromatase expression and secretion of pro-inflammatory cytokines and adipokines in the breast tissue in patients who are obese or overweight. In HER2+ breast tumours, WAT inflammation has been shown to be associated with resistance to trastuzumab mediated via MAPK or PI3K pathways. Furthermore, adipose tissue in patients with obesity is associated with upregulation of immune checkpoints on T-cells that is partially mediated via immunomodulatory effects of leptin and has been paradoxically associated with improved responses to immunotherapy in several cancers. In conclusion, evidence suggests that body composition and metabolic status are associated with patient outcomes. To optimise patient stratification and personalisation of treatment, prospective studies are required to evaluate the role of body composition and metabolic parameters in metabolic immune reprogramming with and without immunotherapy in patients with BC.
Keywords
breast cancer; obesity; inflammation; metabolism; treatment resistance
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Commenter: Constantinos Savva
Commenter's Conflict of Interests: Author