CpG-A and B oligodeoxynucleotides enhance the efficacy of antibody therapy by activating different effector cell populations

Immunostimulatory CpG oligodeoxynucleotides (ODNs) can enhance the therapeutic effect of monoclonal antibodies (mAbs) by enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Distinct classes of CpG ODNs have been found recently to stimulate different effector cell populations. We used murine cancer models to explore the role of various effector cell populations in the antitumor activity seen with mAbs combined with CpG ODNs of the A and B classes. In the 38C13 syngeneic murine lymphoma model, both CpG A and CpG B enhanced the efficacy of murine antilymphoma mAb. Depletion of natural killer (NK) cells alone markedly decreased the efficacy of therapy with mAbs plus CpG A. In contrast, depletion of both NK cells and granulocytes was required to decrease the efficacy of mAb plus CpG B. A human (h) Fc gamma receptor I (FcgammaRI)-expressing transgenic (Tg) mouse model was used to explore the role of FcgammaRI in therapy with mAb and CpG ODN. CpG B induced up-regulation of FcgammaRI in hFcgammaRI Tg mice, whereas CpG A did not. In vitro CpG B also enhanced ADCC of HER-2/neu-expressing tumor cells by the FcgammaRI-directed bispecific antibody MDX-H210 using hFcgammaRI-positive effector cells. In a solid tumor model, tumor growth was inhibited in Tg mice treated with a combination of MDX-H210 and CpG B. These data suggest that CpG A enhance ADCC largely by activating NK cells. In contrast, other effector cell populations, including granulocytes, contribute to the antitumor activity of CpG B and mAbs. FcgammaRI plays an important role in this activity

Sarcomania? The Inapplicability of Sarcopenia Measurement in Predicting Incisional Hernia Development

Background: Incisional hernia is a frequent complication after abdominal surgery. A risk factor for incisional hernia, related to body composition, is obesity. Poor skeletal muscle mass might also be a risk factor, as it may result in weakness of the abdominal wall. However, it remains unknown if sarcopenia (i.e. low skeletal muscle mass) is a risk factor for incisional hernia. Therefore, this study aims to investigate whether a relation between sarcopenia and incisional hernia exists. Methods: Patients from the STITCH trial, who underwent elective midline laparotomy, were included. Computed tomography examinations performed within 3 months preoperatively were used to measure the skeletal muscle index (SMI; cm2/m2). Primarily, SMI measured continuously, sarcopenia based on previously described cut-off values for the SMI, and sarcopenia as the lowest gender-specific SMI quartile were assessed as measures to predict incisional hernia occurrence. Secondary, the association between these three measures and post-operative complications was investigated. Results: In total, 283 patients (45.2% male; mean age 63.7 years; mean BMI 25.36 kg/m2) were included, of whom 52 (18%) devel