Obesity as an immune-modifying factor in cancer immunotherapy

Canter, Robert J.; Le, Catherine T.; Beerthuijzen, Johanna M.T.; Murphy, William J.

doi:10.1002/jlb.5ri1017-401rr

Cited by 28 publications

(29 citation statements)

References 129 publications

(220 reference statements)

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“…236 Of special consideration is cytokine release syndrome or "cytokine storm" and immunotherapy-induced immune-related adverse events (irAEs) that may be potentially exacerbated in obesity, reported in one mouse obesity study in tumor-free mice. 229,247 In our hands, however, immunotherapy does not induce cytokine release syndrome in obese mice with tumors (unpublished observations).…”

Section: Ob E S It Y the MI Crob I Ome And The Ob E S It Y Par Asupporting

confidence: 50%

“…While those studies find an obesity‐ICB efficacy link regardless of sex for most survival measures, one study found the obesity‐associated boost in ICB efficacy for males only 236 . Of special consideration is cytokine release syndrome or “cytokine storm” and immunotherapy‐induced immune‐related adverse events (irAEs) that may be potentially exacerbated in obesity, reported in one mouse obesity study in tumor‐free mice 229,247 . In our hands, however, immunotherapy does not induce cytokine release syndrome in obese mice with tumors (unpublished observations).…”

Section: Obesity the Microbiome And The Obesity Paradox In Immune Cmentioning

confidence: 66%

“…165 Obesity's effects on immunotherapy responses are a critical area of intense research. 229,230 Interestingly, PD-1 and PD-L1 expression on ligandpositive immune cells are increased by obesity, such as on DCs in obese patients. 24,231,232 Accumulation of PD-1+ T-cells is detected in visceral adipose of obese mice and human omental adipose of obese tumor-free patients.…”

Section: Ob E S It Y the MI Crob I Ome And The Ob E S It Y Par Amentioning

confidence: 99%

“…Obesity dramatically changes the immune milieu 165 . Obesity's effects on immunotherapy responses are a critical area of intense research 229,230 . Interestingly, PD‐1 and PD‐L1 expression on ligand‐positive immune cells are increased by obesity, such as on DCs in obese patients 24,231,232 .…”

Section: Obesity the Microbiome And The Obesity Paradox In Immune Cmentioning

confidence: 99%

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Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Sipe

Chaib

Pingili

et al. 2020

Immunological Reviews

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Bile acids (BAs) are known facilitators of nutrient absorption but recent paradigm shifts now recognize BAs as signaling molecules regulating both innate and adaptive immunity. Bile acids are synthesized from cholesterol in the liver with subsequent microbial modification and fermentation adding complexity to pool composition. Bile acids act on several receptors such as Farnesoid X Receptor and the G proteincoupled BA receptor 1 (TGR5). Interestingly, BA receptors (BARs) are expressed on immune cells and activation either by BAs or BAR agonists modulates innate and adaptive immune cell populations skewing their polarization toward a more tolerogenic anti-inflammatory phenotype. Intriguingly, recent evidence also suggests that BAs promote anti-tumor immune response through activation and recruitment of tumoricidal immune cells such as natural killer T cells. These exciting findings have redefined BA signaling in health and disease wherein they may suppress inflammation on the one hand, yet promote anti-tumor immunity on the other hand. In this review, we provide our readers with the most recent understanding of the interaction of BAs with the host microbiome, their effect on innate and adaptive immunity in health and disease with a special focus on obesity, bariatric surgery-induced weight loss, and immune checkpoint blockade in cancer. K E Y W O R D S bariatric surgery, immunometabolism, microbiome, mitochondria, obesity, tumor microenvironment | 221 SIPE Et al.

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Section: Ob E S It Y the MI Crob I Ome And The Ob E S It Y Par Asupporting

confidence: 50%

Section: Obesity the Microbiome And The Obesity Paradox In Immune Cmentioning

confidence: 66%

Section: Ob E S It Y the MI Crob I Ome And The Ob E S It Y Par Amentioning

confidence: 99%

Section: Obesity the Microbiome And The Obesity Paradox In Immune Cmentioning

confidence: 99%

See 2 more Smart Citations

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Sipe

Chaib

Pingili

et al. 2020

Immunological Reviews

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“…Consistent with our finding in HKBC, a recent study reported a significant association between higher expression of CD8+ T-cell signatures and increasing BMI in 1,154 breast cancer patients from the Nurses' Health Study 28 . The link between obesity and breast cancer involves multiple mechanisms that may interplay with each other such as chronic inflammation, estrogen production, growth factor stimulation, and altered metabolism 29 . Future large studies are warranted to follow up this observation.…”

Section: Discussionmentioning

confidence: 99%

Immune gene expression profiling reveals heterogeneity in luminal breast tumors

Zhu

Tse

Wang

et al. 2019

Preprint

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Disease heterogeneity of immune gene expression patterns of luminal breast cancer (BC) has not been well studied. We performed immune gene expression profiling of tumor and adjacent normal tissue in 92 Asian luminal BC patients and identified three distinct immune subtypes. Tumors in one subtype exhibited signs of T-cell activation, lower ESR1/ESR2 expression ratio and higher expression of immune checkpoint genes, nonsynonymous mutation burden, APOBEC-signature mutations, and increasing body mass index compared to other luminal tumors. Tumors in a second subtype were characterized by increased expression of interferonstimulated genes and enrichment for TP53 somatic mutations. The presence of three immune subtypes within luminal BC was replicated in cases drawn from The Cancer Genome Atlas and a Korean breast cancer study. Our findings suggest that immune gene expression and associated genomic features could be useful to further stratify luminal BC beyond the current luminal A/B classification.Introduction:

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Obesity and Survival After Immune Checkpoint Inhibition for Head and Neck Squamous Cell Carcinoma

Mastrolonardo,

Llerena,

et al. 2024

JAMA Otolaryngol Head Neck Surg

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ImportanceFor patients treated with immune checkpoint inhibitors (ICIs), recent data suggest that obesity has a beneficial effect on survival outcomes in various cancer types. Reports on this association in head and neck cancer are limited.ObjectivesTo compare overall survival (OS) to 5 years and functional outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with ICIs based on pretreatment body mass index (BMI).Design, Setting, and ParticipantsThis retrospective population-based cohort study used data obtained from the TriNetX Global Collaborative Network database to identify patients with HNSCC who received ICI treatment between January 1, 2012, and December 31, 2023, resulting in a total of 166 patients (83 with BMI of 20.0-24.9 [normal BMI] and 83 with BMI of ≥30.0 [obesity BMI]) after propensity score matching (PSM) for pretreatment medical comorbidities and oncologic staging.ExposureNormal BMI vs obesity BMI.Main Outcomes and MeasuresOverall survival and functional outcomes (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) were measured to 5 years after ICI treatment and compared between patients with obesity BMI and normal BMI. Additional analyses compared OS and functional outcomes in the cohort with normal BMI and cohorts with overweight BMI (25.0-29.9) and underweight BMI (&lt;20.0).ResultsAmong the 166 patients included in the PSM analysis (112 men [67.1%]; mean [SD] age, 62.9 [15.4] years), obesity BMI was associated with significantly improved OS at 6 months (hazard ratio [HR], 0.54 [95% CI, 0.31-0.96]), 3 years (HR, 0.56 [95% CI, 0.38-0.83]), and 5 years (HR, 0.62 [95% CI, 0.44-0.86]) after ICI treatment, compared with patients with normal BMI. Obesity BMI was also associated with decreased risk of gastrostomy tube dependence at 6 months (odds ratio [OR], 0.41 [95% CI, 0.21-0.80]), 1 year (OR, 0.41 [95% CI, 0.21-0.78]), 3 years (OR, 0.35 [95% CI, 0.18-0.65]), and 5 years (OR, 0.34 [95% CI, 0.18-0.65]). Obesity was also associated with decreased risk for tracheostomy dependence at 1 year (OR, 0.52 [95% CI, 0.28-0.90]), 3 years (OR, 0.45 [95% CI, 0.45-0.90]), and 5 years (OR, 0.45 [95% CI, 0.45-0.90]). There were no differences in rates of dysphagia or immune-related adverse events between cohorts at any points.Conclusions and RelevanceUsing population-level data for patients with HNSCC treated with ICIs, these results suggest that having obesity was associated with improved 6-month, 3-year, and 5-year OS compared with having normal BMI. Additionally, obesity was associated with decreased gastrostomy and tracheostomy tube dependence compared with normal BMI. Further investigation is required to understand the mechanism of these findings.

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Obesity as an immune-modifying factor in cancer immunotherapy

Cited by 28 publications

References 129 publications

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Immune gene expression profiling reveals heterogeneity in luminal breast tumors

Obesity and Survival After Immune Checkpoint Inhibition for Head and Neck Squamous Cell Carcinoma

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