Department of Biology, Massachusetts Institute of Technology, Cambridge, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United States
Ahmed Ali
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United States
Bradley I Reinfeld
Medical Scientist Training Program, Vanderbilt University, Nashville, United States; Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, United States; Graduate Program in Cancer Biology, Vanderbilt University, Nashville, United States
Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
Madelyn D Landis
Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, United States
Rachel A Hongo
Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, United States
Kirsten L Young
Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, United States
Tenzin Kunchok
Whitehead Institute for Biomedical Research, Cambridge, United States
Christopher S Nabel
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States; Department of Medicine, Massachusetts General Hospital, Boston, United States; Harvard Medical School, Boston, United States
Whitehead Institute for Biomedical Research, Cambridge, United States
Johnathan R Kent
Department of Surgery, University of Chicago Medicine, Chicago, United States
Maria Lucia L Madariaga
Department of Surgery, University of Chicago Medicine, Chicago, United States
Rakesh K Jain
Steele Laboratories of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
Kathryn E Beckermann
Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, United States
Caroline A Lewis
Whitehead Institute for Biomedical Research, Cambridge, United States
Clary B Clish
Broad Institute of MIT and Harvard, Cambridge, United States
Ben May Department of Cancer Research, University of Chicago, Chicago, United States
W Kimryn Rathmell
Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, United States; Vanderbilt Center for Immunobiology and Vanderbilt-Ingram Cancer Center, VUMC, Nashville, United States
Vanderbilt Center for Immunobiology and Vanderbilt-Ingram Cancer Center, VUMC, Nashville, United States; Department of Pathology, Microbiology and Immunology, VUMC, Nashville, United States
Department of Biology, Massachusetts Institute of Technology, Cambridge, United States; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United States; Dana-Farber Cancer Institute, Boston, United States
The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients. TIF nutrient composition closely resembles KIF, suggesting that tissue-specific factors unrelated to the presence of cancer exert a stronger influence on nutrient levels than tumor-driven alterations. Notably, select metabolite changes consistent with known features of RCC metabolism are found in RCC TIF, while glucose levels in TIF are not depleted to levels that are lower than those found in KIF. These findings inform tissue nutrient dynamics in RCC, highlighting a dominant role of non-cancer-driven tissue factors in shaping nutrient availability in these tumors.
