Islami, F., Goding Sauer, A., Gapstur, S. M. & Jemal, A. Proportion of cancer cases attributable to excess body weight by US state, 2011–2015. JAMA Oncol. 5, 384–392 (2019).
Sung, H. et al. Global patterns in excess body weight and the associated cancer burden. CA Cancer J. Clin. 69, 88–112 (2019).
Choi, Y. et al. Body mass index and survival in patients with renal cell carcinoma: a clinical-based cohort and meta-analysis. Int. J. Cancer 132, 625–634 (2013).
Hakimi, A. A. et al. An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J. Natl Cancer Inst. 105, 1862–1870 (2013).
Schlesinger, S. et al. Postdiagnosis body mass index and risk of mortality in colorectal cancer survivors: a prospective study and meta-analysis. Cancer Causes Control 25, 1407–1418 (2014).
Wang, Z. et al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat. Med. 25, 141–151 (2019).
Cortellini, A. et al. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable. J. Immunother. Cancer 7, 57 (2019).
Assumpcao, J. A. F., Pasquarelli-do-Nascimento, G., Duarte, M. S. V., Bonamino, M. H. & Magalhaes, K. G. The ambiguous role of obesity in oncology by promoting cancer but boosting antitumor immunotherapy. J. Biomed. Sci. 29, 12 (2022).
Gordon, S. R. et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 545, 495–499 (2017).
Huang, X. et al. PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis. Proc. Natl Acad. Sci. USA 106, 6303–6308 (2009).
Strauss, L. et al. Targeted deletion of PD-1 in myeloid cells induces antitumor immunity. Sci. Immunol. 5, eaay1863 (2020).
Yao, A. et al. Programmed death 1 deficiency induces the polarization of macrophages/microglia to the M1 phenotype after spinal cord injury in mice. Neurotherapeutics 11, 636–650 (2014).
Avgerinos, K. I., Spyrou, N., Mantzoros, C. S. & Dalamaga, M. Obesity and cancer risk: emerging biological mechanisms and perspectives. Metab. Clin. Exp. 92, 121–135 (2019).
Calle, E. E., Rodriguez, C., Walker-Thurmond, K. & Thun, M. J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 348, 1625–1638 (2003).
Dai, Z., Xu, Y. C. & Niu, L. Obesity and colorectal cancer risk: a meta-analysis of cohort studies. World J. Gastroenterol. 13, 4199–4206 (2007).
Murphy, W. J. & Longo, D. L. The surprisingly positive association between obesity and cancer immunotherapy efficacy. JAMA 321, 1247–1248 (2019).
Donnelly, D. et al. The complex relationship between body mass index and response to immune checkpoint inhibition in metastatic melanoma patients. J. Immunother. Cancer 7, 222 (2019).
Naik, G. S. et al. Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition. J. Immunother. Cancer 7, 89 (2019).
Sanchez, A. et al. Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: a cohort study. Lancet Oncol. 21, 283–293 (2020).
Woodall, M. J., Neumann, S., Campbell, K., Pattison, S. T. & Young, S. L. The effects of obesity on anti-cancer immunity and cancer immunotherapy. Cancers 12, 1230 (2020).
Boi, S. K. et al. Obesity diminishes response to PD-1-based immunotherapies in renal cancer. J Immunother. Cancer 8, e000725 (2020).
Lennon, H., Sperrin, M., Badrick, E. & Renehan, A. G. The obesity paradox in cancer: a review. Curr. Oncol. Rep. 18, 56 (2016).
Le, C. T. et al. PD-1 blockade reverses obesity-mediated T cell priming impairment. Front. Immunol. 11, 590568 (2020).
Ringel, A. E. et al. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell 183, 1848–1866 (2020).
Chakarov, S., Bleriot, C. & Ginhoux, F. Role of adipose tissue macrophages in obesity-related disorders. J. Exp. Med. 219, e20211948 (2022).
Hamada, K. et al. Obesity strongly promotes growth of mouse MC38 colon cancer in an orthotopic-syngeneic C57BL/6 mouse model. In Vivo 36, 1643–1646 (2022).
Wagner, A. et al. Metabolic modeling of single Th17 cells reveals regulators of autoimmunity. Cell 184, 4168–4185 (2021).
Christofides, A. et al. SHP-2 and PD-1-SHP-2 signaling regulate myeloid cell differentiation and antitumor responses. Nat. Immunol. 24, 55–68 (2023).
Bally, A. P. et al. NF-kappaB regulates PD-1 expression in macrophages. J. Immunol. 194, 4545–4554 (2015).
Obradovic, A. et al. Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages. Cell 184, 2988–3005 (2021).
Pelka, K. et al. Spatially organized multicellular immune hubs in human colorectal cancer. Cell 184, 4734–4752 (2021).
Katzenelenbogen, Y. et al. Coupled scRNA-seq and intracellular protein activity reveal an immunosuppressive role of TREM2 in cancer. Cell 182, 872–885 (2020).
Wolf, E. M., Fingleton, B. & Hasty, A. H. The therapeutic potential of TREM2 in cancer. Front. Oncol. 12, 984193 (2022).
Li, W. et al. Correlation between PD-1/PD-L1 expression and polarization in tumor-associated macrophages: a key player in tumor immunotherapy. Cytokine Growth Factor Rev. 67, 49–57 (2022).
Schmidt, F. M. et al. Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS ONE 10, e0121971 (2015).
Kumar, R. et al. Association of leptin with obesity and insulin resistance. Cureus 12, e12178 (2020).
Zhao, L. et al. A panel of free fatty acid ratios to predict the development of metabolic abnormalities in healthy obese individuals. Sci. Rep. 6, 28418 (2016).
Kono, Y. et al. Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients. BMC Cancer 20, 175 (2020).
Freemerman, A. J. et al. Myeloid Slc2a1-deficient murine model revealed macrophage activation and metabolic phenotype are fueled by GLUT1. J. Immunol. 202, 1265–1286 (2019).
Wang, W. et al. Diabetic hyperglycemia promotes primary tumor progression through glycation-induced tumor extracellular matrix stiffening. Sci. Adv. 8, eabo1673 (2022).
Dudzinski, S. O. et al. Leptin augments antitumor immunity in obesity by repolarizing tumor-associated macrophages. J. Immunol. 207, 3122–3130 (2021).
Reinfeld, B. I. et al. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature 593, 282–288 (2021).
Sorrelle, N. et al. Improved multiplex immunohistochemistry for immune microenvironment evaluation of mouse formalin-fixed, paraffin-embedded tissues. J. Immunol. 202, 292–299 (2019).
Zhang, L. et al. Single-cell analyses inform mechanisms of myeloid-targeted therapies in colon cancer. Cell 181, 442–459 (2020).
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021).
Finak, G. et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 16, 278 (2015).
