Obesity Does Not Exacerbate the Protumorigenic Systemic Environment in Sarcoma Subjects

Abstract

Sarcomas are a rare but fatal tumor type that accounts for <1% of adult solid malignancies and ~15% of childhood malignancies. Although the use of immunotherapy is being actively investigated for other solid tumors, advances in immunotherapy for sarcoma patients are lacking. To better understand the systemic immune environment in sarcoma patients, we performed a detailed multiplex analysis of serum cytokines, chemokines, and protumorigenic factors from treatment-naive subjects with localized, high-grade sarcoma. Because obesity is a major healthcare issue in the United States, we additionally examined the effects of obesity on serum protein profiles in our sarcoma subject cohort. We found that the systemic host environment is profoundly altered to favor tumor progression, with epidermal growth factor, angiopoietin-2, vascular endothelial growth factor A, IL-6, IL-8, and MIP-1β all increased relative to tumor-free controls (all p < 0.05). Surprisingly, we found that obesity did not exacerbate this protumorigenic profile, as epidermal growth factor and IL-8 decreased with increasing subject body mass index (both p < 0.05 versus normal or overweight subjects). The Th2-related cytokines IL-4, IL-5, and IL-13 were also decreased in the presence of obesity. Thus, although the systemic environment in sarcoma subjects favors tumor progression, obesity does not further aggravate the production of protumorigenic factors.

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

“…Histopathologically, sarcomas are classified as either bone or soft tissue sarcomas [ 3 ]. To date, the etiology of sarcomas is not well characterized; however, their incidence appears to be associated with heredity [ 4 ], viral infection [ 5 ], trauma [ 6 ], environmental factors [ 7 ], and exposure to radiation [ 8 ]. Compared with other cancers, the degree of malignancy of sarcomas is relatively high [ 9 ], and hematogenous metastasis can spread to various organs, such as lung, brain, liver, and bone [ 10 , 11 ].…”

Obesity induces limited changes to systemic and local immune profiles in treatment-naive human clear cell renal cell carcinoma

“…Our prior studies using an orthotopic murine renal cancer model revealed that immune dysfunction was exacerbated in mice with diet-induced obesity [9,11]. However, despite numerous pre-clinical results indicating that obesity promotes tumor progression via multiple detrimental effects on the immune system, our retrospective examination of human sarcoma subjects revealed that obesity had surprisingly limited effects on plasma cytokine and chemokine profiles, leading us to conclude that obesity, as measured by BMI, did not exacerbate the pro-tumorigenic systemic environment in treatment-naive individuals with sarcoma [16].…”

Early Radiation-Induced Sarcoma in an Adolescent Treated for Relapsed Hodgkin Lymphoma with Nivolumab

“…Some studies showed that excessive amounts of adipose tissue promoted resistances of leukemic cells to chemotherapy and facilitated tumor spread [21,23]. In contrast, in sarcoma patients, obesity did not appear to exacerbate the protumorigenic environment and aggravate a predisposition to tumor progression [24]. A recent case-control study suggested that obesity during childhood cancer treatment might be associated with increased risk for SMNs [25].…”