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Re-Evaluating the Effects of Obesity on Cancer Immunotherapy Outcomes in Renal Cancer: What Do We Really Know?
Kristine I Farag1, Amani Makkouk2, Lyse A Norian3,4,5
1Science and Technology Honors Program, University of Alabama at Birmingham, Birmingham, AL, United States.
Abstract:
Obesity has reached global epidemic proportions and its effects on interactions between the immune system and malignancies, particularly as related to cancer immunotherapy outcomes, have come under increasing scrutiny. Although the vast majority of pre-clinical murine studies suggest that host obesity should have detrimental effects on anti-tumor immunity and cancer immunotherapy outcomes, the opposite has been found in multiple retrospective human studies. As a result, acceptance of the "obesity paradox" paradigm, wherein obesity increases cancer risk but then improves patient outcomes, has become widespread. However, results to the contrary do exist and the biological mechanisms that promote beneficial obesity-associated outcomes remain unclear. Here, we highlight discrepancies in the literature regarding the obesity paradox for cancer immunotherapy outcomes, with a particular focus on renal cancer. We also discuss multiple factors that may impact research findings and warrant renewed research attention in future studies. We propose that specific cancer patient populations may be affected in fundamentally different ways by host obesity, leading to divergent effects on anti-tumor immunity and/or immunotherapy outcomes. Continued, thoughtful analysis of this critical issue is therefore needed to permit a more nuanced understanding of the complex effects of host obesity on cancer immunotherapy outcomes in patients with renal cancer or other malignancies.
Insights
Obesity
Area of Science:
- Oncology
- Immunology
- Metabolism
Background:
- Obesity is a global epidemic impacting cancer development and treatment.
- The relationship between obesity, immunity, and cancer immunotherapy outcomes is complex and debated.
- Pre-clinical studies often contradict human observational data regarding obesity's effect on anti-tumor immunity.
Purpose of the Study:
- To review discrepancies in the literature regarding the obesity paradox in cancer immunotherapy.
- To focus on the specific context of renal cancer and its interaction with obesity.
- To identify factors influencing research findings and suggest future research directions.
Main Methods:
- Literature review and critical analysis of existing studies on obesity and cancer immunotherapy.
- Examination of pre-clinical (murine) versus retrospective human studies.
- Discussion of potential biological mechanisms and confounding factors.
Main Results:
- Conflicting evidence exists regarding obesity's impact on anti-tumor immunity and immunotherapy efficacy.
- The "obesity paradox" (obesity worsening cancer risk but improving outcomes) is widely discussed but not universally supported.
- Human studies often show improved immunotherapy outcomes in obese patients, contrary to animal models.
Conclusions:
- The effects of obesity on cancer immunotherapy are not uniform and may vary by patient population.
- Biological mechanisms underlying the "obesity paradox" in cancer immunotherapy remain unclear.
- Further research is needed to understand how obesity influences anti-tumor immunity and immunotherapy outcomes in specific cancers like renal cancer.
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