Human Prostate Cancer Infiltrating Lymphocytes: Raft Microdomains, Signaling and Activation in Organ Cultures
Abstract
Prostate cancer is the second leading cause of malignancy-related mortality in males in the Western world. While radical prostatectomy and local radiotherapy are largely successful for patients with localized cancer, available treatments for metastatic prostate carcinoma have demonstrated weak curative efficacy. Thus, androgen reduction often results in the selection of hormone-resistant clones, which seem to be also resistant to radiotherapy or chemotherapy. It is therefore necessary to find alternative therapeutic approaches to hormone-refractory metastatic prostate cancer. Immunotherapy consists in harnessing the immune system to fight cancer and may represent a valid alternative therapy for patients. Cellular immunotherapy consists of giving the patient cells that stimulate anti-tumor activity (tumor and dendritic cell vaccines) or that have intrinsic anti-tumor activity (autologous and allogeneic lymphocytes). However, these approaches have achieved only limited success against established cancer in humans. The fact that human cancers are usually not spontaneously eliminated, together with the modest success of human experimental immunotherapies, has sparked interest in understanding the basis for inadequate anti-tumor immune responses. Our study has demonstrated that human prostate cancers are infiltrated by "armed" cytotoxic lymphocytes, i.e .the cells mainly involved in killing of tumor cell. However, these effector cells are inactive because "narcotized" by the tumor environment. We proved that by inhibiting the activity of two enzymes, arginase(ARG) and nitric oxide synthase (NOS), that are highly expressed in tumor but not in normal prostatic tissue, it was possible to rouse lymphocytes and induce cancer cell death. These results identify a novel and dominant mechanism by which prostate cancer suppress immune responses in situ and suggest novel strategies for tumor immunotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2006
- Accession Number
- ADA471637
Entities
People
- Antonella Viola