In spite of major research efforts, the treatment of advanced non-small cell lung cancer is still largely inefficient. Indeed, this cancer type has a poor prognosis, and no curative therapies are available. Over the last years, it has been become increasingly clear that (relatively) successful chemotherapies such as the anthracycline-based neoadjuvant treatment of locally advanced breast cancer...

Cancer is associated with immune dysfunction characterized by the presence of proinflammatory and immunosuppressive cells and factors that contribute to tumor growth and progression. Here we show that mammary tumor growth is associated with defects in hematopoiesis, leading to myeloproliferative-like disease (leukemoid reaction), anemia, and disruption of the bonemarrow stem/progenitor compartm...

R esearchers at the University of Pittsburgh Cancer Institute (UPCI), employing a new strategy to hunt for human viruses, have discovered a previously unknown virus strongly associated with a rare but deadly skin cancer called Merkel cell carcinoma. The strategy was described in a recent issue of the journal Science by UPCI’s Yuan Chang, Patrick Moore, Huichen Feng, and Masahiro Shuda. This is ...

Westerlund et al. (1) conclude that HIF-2α is linked to neuroblastoma suppression, contradicting several previous observations and current views of the role of HIF-2 in tumorigenesis. We believe that their conclusions are based on flawed cellular models and inappropriate interpretations of their own and public neuroblastoma expression data, as detailed below. First, HIF proteins are continuousl...

Purpose: Immunocytokine (IC) hu14.18-IL2 is a fusion protein of humanized antidisialoganglioside (GD2) antibody (hu14.18) and interleukin (IL)-2. Sixty-one melanoma and neuroblastoma patients received IC in phase I/Ib studies. Patient sera were examined in ELISA to determine if an anti-IC antibody response occurred during treatment. Experimental Design: Serum was assayed for anti-idiotypic anti...

Elevated levels of TGFb are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFb pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFb remains challenging because TGFb has tumor suppressor functions in many epithelial malignancies, including pancreatic cancer. In fact, direct neutralization ...

The potential for effective immune therapy for cancer has been met with considerable enthusiasm because of a number of fundamental advances in our understanding of the immune responses to cancer. First, previous questions about the existence of tumor antigens have largely been answered, since tumorassociated and tumor-specific antigens clearly exist and, when they are recognized by antigen-spec...

Purpose: Mesothelin is a glycoprotein expressed on normal mesothelial cells and is overexpressed in several histologic types of tumors including pancreatic adenocarcinomas. A soluble form of mesothelin has been detected in patients with ovarian cancer and malignant mesothelioma, and has prognostic value. Mesothelin has also been considered as a target for immune-based therapies. We conducted a ...

The relationship between tumor-associated macrophages (TAM) and epithelial-to-mesenchymal transition (EMT) during the initiation and progression of metastasis is still unclear. Here, a role for the vitamin D receptor (VDR) in metastasis was identified, as well as a role in the relationship between TAMs and EMT. First, the expression level of VDRwas examined in clinical tissue fromhuman patients...

Active suppression of tumor-specific T lymphocytes can limit both immune surveillance and immunotherapy. Several mouse tumors, either transplantable or spontaneously arising, alter the normal myelopoiesis and cause the expansion of a population of CD11b+/Gr-1+ cells in the blood, lymphoid organs and at the tumor site. These cells were recently defined as myeloid-derived suppressor cells (MDSCs)...