BioProject

Tumors can occur in many sites in the body, but how tissues at different anatomical sites affect tumor microenvironments and their subsequent response to therapy is not known. More...

Tumors can occur in many sites in the body, but how tissues at different anatomical sites affect tumor microenvironments and their subsequent response to therapy is not known. Here we show that different tissues can cause the same tumor to develop fundamentally different microenvironments resulting in dramatic changes in responses to immunotherapy. Whereas established subcutaneous tumors could be eradicated in the majority of mice using a combination of three agonist antibodies, tumors in visceral organs responded much less. Orthotopic kidney tumors had a microenvironment with a higher frequency of alternatively-activated macrophages and their associated molecules. Neutralizing the CCL2 chemokine or IL-13 cytokine, important in macrophage biology led to a greatly improved therapeutic effect. Importantly, a significantly reduced therapeutic response of subcutaneous tumors was observed when visceral tumors were simultaneously present in the same mice. In this study we sought to compare gene expression of mouse renal cell carcinoma cells growing in the kidney to cells growing subcutaneously. Renca is a renal cell carcinoma cell line (Murphy and Hrushesky, 1973). To produce subcutaneous tumors, mice received 2 x 10^5 Renca. Orthotopic tumors were established by first surgically isolating the organ and then injecting 2 x 10^5 Renca cells intrakidney (IK) into the outer cortex of the kidney in 20 ul of PBS. Tumors were removed from mice 12 days after implantation, when approximately 20-30 mm2. Tumors were snap frozen on liquid nitrogen prior to processing for total RNA followed by analysis on Mouse Gene 1.0 chips. Overall design: Kidney Renca tumors were excised from 3 BALB/c mice and subcutaneous Renca tumors were excised from another 3 BALB/c mice. cDNA was prepared and hybridized to Mouse Gene 1.0 ST chips. Less...