RESUMEN
PURPOSE: Metastatic malignant melanoma is a devastating disease with a poor prognosis. Recent therapeutic trials have focused on immunotherapy to induce development of endogenous antitumor immune responses. To date, such protocols have shown success in activation of tumor-specific CTL but no overall improvement in survival. To kill tumor, antigen-specific CTL must efficiently target and enter tumor tissue. The purpose of this study was to examine the pathway of leukocyte migration to metastatic melanoma. EXPERIMENTAL DESIGN: Peripheral blood and metastatic melanoma tissues (n = 65) were evaluated for expression of adhesion molecules using immunohistochemistry of tumor sections and flow cytometry of tumor-associated and peripheral blood CTL and compared with healthy controls. CTL expressing T-cell receptors for the melanoma antigen MART-1 were identified in a subset of samples by reactivity with HLA-A2 tetramers loaded with MART-1 peptide. RESULTS: Results show that the majority of metastatic melanoma samples examined do not express the vascular adhesion receptors E-selectin (CD62E), P-selectin (CD62P), and intercellular adhesion molecule-1 (CD54) on vessels within the tumor boundaries. Strong adhesion receptor expression was noted on vessels within adjacent tissue. Tumor-associated T lymphocytes accumulate preferentially in these adjacent areas and are not enriched for skin- or lymph node-homing receptor phenotype. CONCLUSION: Expression of leukocyte homing receptors is dysregulated on the vasculature of metastatic melanoma. This results in a block to recruitment of activated tumor-specific CTL to melanoma metastases and is a likely factor limiting the effectiveness of current immunotherapy protocols.
Asunto(s)
Linfocitos Infiltrantes de Tumor/inmunología , Melanoma/secundario , Receptores Mensajeros de Linfocitos/metabolismo , Neoplasias Cutáneas/patología , Linfocitos T Citotóxicos/inmunología , Antígenos de Neoplasias/análisis , Antígenos CD8/análisis , Adhesión Celular , Selectina E/análisis , Selectina E/metabolismo , Humanos , Molécula 1 de Adhesión Intercelular/análisis , Molécula 1 de Adhesión Intercelular/metabolismo , Antígeno MART-1 , Melanoma/química , Melanoma/inmunología , Proteínas de Neoplasias/análisis , Selectina-P/análisis , Selectina-P/metabolismo , Receptores de Antígenos de Linfocitos T/análisis , Receptores Mensajeros de Linfocitos/análisis , Neoplasias Cutáneas/química , Neoplasias Cutáneas/inmunologíaRESUMEN
OBJECTIVES: To estimate the prevalence of complementary and alternative medicine (CAM) usage among emergency department (ED) patients. METHODS: This study was a cross-sectional study in four Boston-area EDs. For two 24-hour periods, the authors interviewed consecutive patients age 18 and older about whether they had ever used or had recently (within the past year) used CAM "remedies" (e.g., herbal treatments) or "therapies" (e.g., chiropractic). The authors also asked about the patient's disclosure of CAM usage to allopathic health care providers. RESULTS: Of 978 patients, 752 patients were eligible. Among these, 539 (72%) were interviewed. Of these patients, ever having used CAM was reported by 57% (95% CI = 52% to 61%), and 37% (95% CI = 33% to 41%) reported use in the past year. In a multivariate model of recent CAM usage, independent predictors were younger age, higher education level, and chronic pain. Patients who spoke Spanish as their primary language were less likely to report CAM usage. Disclosure of CAM usage to allopathic providers was low, yet >80% reported that they would be comfortable discussing their CAM usage with allopathic providers. CONCLUSIONS: CAM usage was common among ED patients enrolled in our study, despite underreporting to ED staff. Given the growing evidence of benefits and hazards from popular CAM remedies and therapies, ED staff should consider raising this health issue with their patients.