Abstract 4710: Tumor-infiltrating immune cells in gastrointestinal stromal tumors (GIST) related to the response to tyrosine kinase inhibitor therapy

Purpose: The prognostic predictors for neoadjuvant and palliative tyrosine kinase inhibitor (TKI) effect in GIST patients are few beyond mutational status. We analyzed the extent and composition of tumor-infiltrating immune cells in GIST after different TKI therapeutic regimens and response. Methods: From 60 GIST patients, surgical specimens were available and divided into six different groups of 10 cases each, with the primary tumors graded for malignant behaviour acc. to Miettinen&Lasota 2006. In the neoadjuvant groups all tumors were biopsy proven and had documented IM-sensitive mutations in the KIT receptor. low risk gastric GIST high risk GIST of the small bowel locally advanced GIST after neoadjuvant imatinib (IM) with 30% of viable cells remaining progressive liver metastases resistant to ≥2 TKI inhibitors progressive peritoneal mets. resistant to ≥2 TKI inhibitors. We used 2-μm sections of formalin-fixed, paraffin-embedded tissue samples for immunohistochemistry with the used Dako REAL EnVision Detection System (K5007, Dako) and Anti-CD68 (Dako); Anti-CD11c (Abcam); Anti-CD163 (Leica); Anti-CD11b (Abcam); Anti-CD4 (Leica); Anti-CD8(Leica); Anti-FOXP3 (Abcam) antibodies. The phenotypes of immune cells were compared in the defined GIST groups. Recurrence-free survival (RFS) was evaluated in neoadjuvant and overall-survivals (OS) after TKI failure was measured in TKI resistant M1 patients . Results: The rate of CD11c+ M1 macrophages is higher in low-risk GISTs compared to high risk GISTs, but CD11b+ myeloid cells are exactly the opposite. Foxp3+ Tregs, CD163+ M2 macrophages and CD11b+ myeloid cells are significantly higher in TKI resistance or neoadjuvant (viable cells>30%) tissues compared with neoadjuvant (viable cells