Summary We studied the effectiveness of monoclonal anti‐CD40 + cytosine–phosphate–guanosine‐containing oligodeoxynucleotide 1826 (CpG‐ODN) immunotherapy (IT) in mice treated with multidrug chemotherapy (CT) consisting of vincristine, cyclophosphamide and doxorubicin. Combining CT with IT led to synergistic anti‐tumour effects in C57BL/6 mice with established B16 melanoma or 9464D neuroblastoma. CT suppressed the functions of T cells and natural killer (NK) cells, but primed naïve peritoneal macrophages (Mφ) to in vitro stimulation with lipopolysaccharide (LPS), resulting in augmented nitric oxide (NO) production. IT, given after CT, did not restore the responsiveness of T cells and NK cells, but further activated Mφ to secrete NO, interferon‐γ (IFN‐γ) and interleukin (IL)‐12p40 and to suppress the proliferation of tumour cells in vitro. These functional changes were accompanied by immunophenotype alterations on Mφ, including the up‐regulation of Gr‐1. CD11b+ F4/80+ Mφ comprised the major population of B16 tumour‐infiltrating leucocytes. CT + IT treatment up‐regulated molecules associated with the M1 effector Mφ phenotype [CD40, CD80, CD86, major histocompatibility complex (MHC) class II, IFN‐γ, tumour necrosis factor‐α (TNF‐α) and IL‐12] and down‐regulated molecules associated with the M2 inhibitory Mφ phenotype (IL‐4Rα, B7‐H1, IL‐4 and IL‐10) on the tumour‐associated Mφ compared with untreated controls. Together, the results show that CT and anti‐CD40 + CpG‐ODN IT synergize in the induction of anti‐tumour effects which are associated with the phenotypic repolarization of tumour‐associated Mφ.

The hu14.18-IL2 (EMD 273063) IC, consisting of a GD(2)-specific mAb genetically engineered to two molecules of IL-2, is in clinical trials for treatment of GD(2)-expressing tumors. Anti-tumor activity of IC in vivo and in vitro involves NK cells. We studied the kinetics of retention of IC on the surface of human CD25(+)CD16(-) NK cell lines (NKL and RL12) and GD(2)(+) M21 melanoma after IC binding to the cells via IL-2R and GD(2), respectively. For NK cells, ∼ 50% of IC was internalized by 3 h and ∼ 90% by 24 h of cell culture. The decrease of surface IC levels on NK cells correlated with the loss of their ability to bind to tumor cells and mediate antibody-dependent cellular cytotoxicity in vitro. Unlike NK cells, M21 cells retained ∼ 70% of IC on the surface following 24 h of culture and maintained the ability to become conjugated and lysed by NK cells. When NKL cells were injected into M21-bearing SCID mice, IT delivery of IC augmented NK cell migration into the tumor. These studies demonstrate that once IC binds to the tumor, it is present on the tumor surface for a prolonged time, inducing the recruitment of NK cells to the tumor site, followed by tumor cell killing.

Clinical trials are leading the charge for substantial gains toward personalized treatment of aggressive endometrial carcinoma subtypes.

Introduction: Gastritis cystica profunda (GCP) is a rare tumor which occurs more commonly in patients with prior gastric surgery. The nonspecific symptoms and radiographic appearance of this tumor mimic that of other hyperproliferative conditions making diagnosis difficult without definitive surgical resection. This report provides a comprehensive review of GCP and all GCP cases reported to date. Methods: A comprehensive literature search (1972-2011) was conducted with all reported GCP cases analyzed. Keywords searched included gastritis cystica profunda, submucosal cysts of the stomach, and heterotopic submucosal gastric glands. Results: Thirty-seven GCP cases have been reported since 1972, which includes 29 (78%) men and 8 (21%) women (M:F ratio, 3.6:1). The overall mean age was 60.5 years (range, 39 -81 years) with 55.6 years (range, 39 -79) and 62.2 years (range, 39 -81 years) in women and men, respectively. 65% (N = 24) had prior gastric surgery. 62% (N = 23) of GCP tumors were located in the body; 24% (N = 9) in the fundus; 8% (N = 3) in the antrum; or 6% (N = 2) in the cardia of the stomach. GCP was an incidental finding in 19% of patients. Complete excision was performed most often (73%) followed by endomucosal resection (18%), and polypectomy (4.5%). One patient underwent surveillance (4.5%). Conclusions: GCP is a rare gastric tumor, which is difficult to diagnose preoperatively and masquerades as a malignancy. GCP is more common in men and typically presents with nonspecific symptoms. Although a benign lesion, GCP may represent an intermediate histology in the malignant progression to gastric neoplasia. To date, there have been no reports of local recurrence or distant metastasis following definitive surgical excision, which remains the standard of care.

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