Immune Function in Obesity and Cancer

The interplay between obesity-associated immune dysfunction and cancer pathogenesis has become a major focus of translational research. Adipose tissue in obesity secretes a range of adipokines that drive chronic low-grade inflammation and alter the metabolic programming of innate and adaptive immune cells. This inflammatory milieu shifts macrophages towards a pro-inflammatory M1 phenotype, impairs dendritic cell antigen presentation and diminishes natural killer cell cytotoxicity, while promoting expansion of myeloid-derived suppressor cells that inhibit T cell activity. In parallel, CD8+ T lymphocytes in obese hosts experience heightened metabolic stress, leading to accelerated exhaustion and reduced effector function. These convergent processes not only elevate cancer incidence and progression in obese individuals but also paradoxically influence responses to immune checkpoint therapies. A nuanced understanding of the molecular and cellular networks linking adiposity to antitumour immunity is essential for guiding prevention strategies and optimising immunotherapeutic regimens.

Research from Nature Portfolio

One key study in a murine breast cancer model has demonstrated that a high-fat diet promotes the conversion of non-exhausted CD8+ T cells into a PD-1+ exhausted phenotype within developing tumours. Exhausted T cells displayed diminished expression of cytotoxic mediators alongside upregulation of tumour-trophic genes, establishing a direct mechanistic link between metabolic stress induced by obesity and impaired T cell–mediated immunosurveillance. This work highlights potential metabolic checkpoints for restoring T cell function in obese cancer patients.

Immune Function in Obesity and Cancer publication trend

The graph below shows the total number of articles in immune function in obesity and cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Adipokine: A bioactive molecule secreted by adipose tissue that modulates immune and metabolic signalling.

Chronic low-grade inflammation: A persistent, systemic inflammatory state characterised by modest elevations of cytokines and immune activation.

Checkpoint blockade: A form of immunotherapy that inhibits regulatory receptors on T cells to enhance antitumour responses.

Myeloid-derived suppressor cell (MDSC): A heterogeneous population of immature myeloid cells that suppress T cell function within tumours and peripheral tissues.

T cell exhaustion: A dysfunctional state of effector T cells marked by loss of proliferative capacity and expression of inhibitory receptors.

Tumour microenvironment: The complex milieu of immune cells, stromal components and signalling molecules surrounding a tumour.

Natural killer (NK) cell: An innate lymphocyte subset capable of rapid cytotoxicity and cytokine production against transformed or infected cells.

References

1. Multifaceted effects of obesity on cancer immunotherapies: Bridging preclinical models and clinical data. Seminars in Cancer Biology (2023).
2. The Effects of Obesity on Anti-Cancer Immunity and Cancer Immunotherapy. Cancers (2020).
3. Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer. Frontiers in Immunology (2020).
4. The Obesity Paradox in Cancer, Tumor Immunology, and Immunotherapy: Potential Therapeutic Implications in Triple Negative Breast Cancer. Frontiers in Immunology (2019).
5. Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis. Scientific Reports (2019).
6. Obesity-Associated Myeloid-Derived Suppressor Cells Promote Apoptosis of Tumor-Infiltrating CD8 T Cells and Immunotherapy Resistance in Breast Cancer. Frontiers in Immunology (2020).