Oncolytic Sindbis virus targets tumors defective in the interferon response and induces significant bystander antitumor immunity in vivo.

Sindbis virus (SBV) has been shown to possess oncolytic potential in many human xenograft tumor models in immunocompromised mice. However, the mechanism underlying the tumor selectivity of SBV remains undetermined. In this study, we provide evidence that the tumor tropism of SBV infection is not determined by the levels of SBV receptor but by the status of the type I interferon (IFN) response in the tumors. Our results demonstrate that cells with defects in the IFN response (in either IFN-ß production or IFN signaling) were highly susceptible to SBV infection in vitro. The results of oncolysis experiments conducted in immunocompetent animals further confirmed that the success of SBV-mediated oncolysis is greatly dependent on the presence of defects in IFN signaling in tumors. In all cases, viral titers rapidly declined in tumors due to host immune responses in immunocompetent animals. Interestingly, however, tumor-specific immune responses were concomitantly elicited, which might contribute to the sustained antitumor effect observed after the clearance of SBV. These findings indicate that SBV-mediated virotherapy is a promising therapeutic strategy for cancers defective in the IFN response and underscore the importance of bystander antitumor immunity in the efficacy of this virotherapy.

Mycobacterial spindle cell pseudotumor of skin.

Spindle cell pseudotumors may occur due to mycobacterial infection in immunocompromised hosts, particularly those with acquired immunodeficiency syndrome (AIDS). Most of the reported mycobacterial spindle cell pseudotumors were found in the lymph nodes. We report a case of spindle cell pseudotumor in a 37-year-old man with AIDS who presented with a firm nodule over his right arm. Histologically, the tumor was composed of proliferative spindle cells admixed with histiocytes and inflammatory cells. Ziehl-Neelsen stain revealed many acid-fast bacilli in the spindle cells and histiocytes. The acid-fast bacilli were shown to be Mycobacterium avium intracellulare by culture and sequencing of the polymerase chain reaction product of mycobacterial 65-kDa heat shock protein gene. Immunohistochemically, the spindle cells were reactive to CD68, suggesting macrophage differentiation of these cells. It is important for pathologists to recognize this unusual manifestation of mycobacterial infection in immunocompromised patients and avoid mistaking the lesion for a mesenchymal neoplasm.