Association of minimally invasive colorectal resection with elevated levels of plasma B7 homolog 1 (B7-H1) during the first month after surgery and effect on immune suppression and growth of residual metastases.

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602 Background: The co-stimulatory molecule B7 homolog 1 (B7-H1) is a ligand for PD-1 which is an immunoinhibitory receptor of activated lymphocytes. PD-1 expression is upregulated on tumor infiltrating lymphocytes (TILs), and B7-H1 expressed on cancer cells may inhibit T-cell activation and proliferation. B7-H1 is also expressed on endothelial (EC) and intestinal epithelial cells as well as activated macrophages. B7H1 in EC is rapidly induced by IFN-gamma and TNF. B7-H1 silencing with siRNA inhibits tumor cell proliferation/invasion. B7H1 expression in keratinocytes (KC) directly downregulates CD8(+) T-cell effector function via PD-1 binding at sites of inflammation. Shed B7-H1 can be found in the blood. Surgery’s impact on plasma B7H1 levels is unknown. This study’s purpose was to evaluate plasma B7H1 levels during the first month after MICR for colorectal (CRC). Methods: MICR CRC patients in an IRB approved data/plasma bank with adequate plasma available were eligible. Clinical and pathological data were reviewed. Blood samples were collected preoperatively (PreOp) and at 6 post-operative (Postop) time points (POD 1, 3, 7-13, 14-20, 21-27, 28-41). B7-H1 levels were analyzed in duplicate using ELISA. The Wilcoxon test was used for analysis. Results: 88 CRC patients who had a MICR met inclusion criteria (28% rectal and 62% colon lesions). The mean PreOp B7-H1 level was 51.9±20.9 pg/ml. Significantly elevated mean plasma levels were noted on POD1 (64.9±24.2 pg/ml, n = 86, p = < 0.0001), POD3 (67.3±24.6 pg/ml, n= 72, p = < 0.0001), POD7-13 (69.2±22.6 pg/ml, n = 65, p = < 0.0001), POD14-20 (72.5±28.9 pg/ml, n=23,p=0.001), POD 21-27 (79.4±66.6 pg/ml, n = 13, p = 0.001), and on POD 28-41 (56.3 ±22.7 pg/ml, n = 20, p =0.02), when compared to PreOp levels. Conclusions: Plasma B7-H1 levels are elevated for over a month after MICR for CRC. The etiology of the early increase may be the acute inflammatory response whereas late elevations may be related to wound healing-related tissue remodeling. Elevated plasma B7-H1 may suppress TIL’s which may result in increased tumor growth. Further studies are warranted.