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Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer.

ABSTRACT: Immune checkpoint blockade (ICB) has improved outcomes in some cancers. A major limitation of ICB is that most patients fail to respond, which is partly attributable to immunosuppression. Obesity appears to improve immune checkpoint therapies in some cancers, but impacts on breast cancer (BC) remain unknown. In lean and obese mice, tumor progression and immune reprogramming were quantified in BC tumors treated with anti-programmed death-1 (PD-1) or control. Obesity augments tumor incidence and progression. Anti-PD-1 induces regression in lean mice and potently abrogates progression in obese mice. BC primes systemic immunity to be highly responsive to obesity, leading to greater immunosuppression, which may explain greater anti-PD-1 efficacy. Anti-PD-1 significantly reinvigorates antitumor immunity despite persistent obesity. Laminin subunit beta-2 (Lamb2), downregulated by anti-PD-1, significantly predicts patient survival. Lastly, a microbial signature associated with anti-PD-1 efficacy is identified. Thus, anti-PD-1 is highly efficacious in obese mice by reinvigorating durable antitumor immunity. VIDEO ABSTRACT.

SUBMITTER: Pingili AK

PROVIDER: S-EPMC8574993 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer

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Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer [tumor]

Project description:Immune checkpoint blockade (ICB) has improved outcomes in some cancers. A major limitation of ICB is that a majority of patients fail to respond, which is partly attributable to immunosuppression. Obesity appears to improve immune checkpoint therapies in some cancers but impacts on breast cancer (BC) remain unknown. In obese mice fed an obesogenic or lean controls on a low fat diet, mice are injected with BC cells andtreated with anti-PD-1 or control. Obesity leads to immunosuppression systemically in tumor-free mice that is exacerbated in tumor-bearing mice. Obesity augments tumor incidence and progression. Anti-PD-1 induces regression in lean mice and potently abrogates progression in obese mice. Anti PD-1 significantly reduces immunosuppressive cells and elevates anti-tumor immune cells. Lamb2, downregulated by anti-PD1, significantly predict patient survival. Last, we identify a microbial signature associated with anti-PD-1 efficacy. In sum, anti-PD-1 is highly efficacious in obese mice by reinvigorating durable antitumor immunity.

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Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer [tumor]

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Ablative Radiotherapy Reprograms the Tumor Microenvironment of a Pancreatic Tumor in Favoring the Immune Checkpoint Blockade Therapy.

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