Purpose of Review Obesity is a recognized risk factor for the development of breast cancer and recurrence even when patients are treated appropriately. We reviewed the literature that addresses the impact of obesity on diagnosis and the individual therapeutic interventions, and present a summary of the findings. Recent Findings Compared to non-obese women with breast cancer, obese women with breast cancer have a worse disease-free and overall survival despite appropriate local and systemic therapies. In brief, obese breast cancer patients experience more complications related to surgery, radiation, and chemotherapy. Further, obese patients are at increased risk for local recurrence compared to normal-weight women. Similarly, systemic chemotherapy is less effective, even when dosed appropriately on the basis of actual weight. Overall, endocrine therapy is less effective in obese women, and there is a suggestion that aromatase inhibitors may be selectively less effective than tamoxifen. Obese women are less likely to undergo breast reconstruction than normal-weight women, and those who do have surgery experience more surgical complications. Summary The efficacy of cancer treatments is significantly lower in obese breast cancer survivors, posing greater challenges in patient care and disease management in this patient population. Further investigations are warranted to assess the effects on treatment outcomes and optimize therapeutic mechanisms in order to successfully target breast cancer associated with obesity.

Functional CD8⁺T cells in human tumors play a clear role in clinical prognosis and response to immunotherapeutic interventions. PD-1 expression in T cells involved in chronic infections and tumors such as melanoma often correlates with a state of T-cell exhaustion. Here we interrogate CD8⁺tumor-infiltrating lymphocytes (TILs) from human breast and melanoma tumors to explore their functional state. Despite expression of exhaustion hallmarks, such as PD-1 expression, human breast tumor CD8⁺TILs retain robust capacity for production of effector cytokines and degranulation capacity. In contrast, melanoma CD8⁺TILs display dramatic reduction of cytokine production and degranulation capacity. We show that CD8⁺TILs from human breast tumors can potently kill cancer cells via bi-specific antibodies. Our data demonstrate that CD8⁺TILs in human breast tumors retain polyfunctionality, despite PD-1 expression, and suggest that they may be harnessed for effective immunotherapies.

Dysregulated inflammation in adipose tissue, marked by increased proinflammatory T-cell accumulation and reduced regulatory T cells (Tregs), contributes to obesity-associated insulin resistance. The molecular mechanisms underlying T-cell-mediated inflammation in adipose tissue remain largely unknown, however. Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. Stat3 activity is elevated in obese VAT and in VAT-resident T cells. Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. In addition, Stat3 in T cells in DIO mice affects adipose tissue macrophage accumulation and M2 phenotype. Our study identifies Stat3 in VAT-resident T cells as an important mediator and direct target for regulating adipose tissue inflammation, DIO, and its associated metabolic dysfunctions.