Tumor-Infiltrating Lymphocytes Express Vascular Endothelial Growth Factor in Renal Cell Carcinomas

Abstract

Background: Known influence of the immune system on metastases of renal cell cancer (RCC) has led to the development of several therapeutic approaches for further stimulation of the host immune system by cytokines and the retransfusion of tumor-infiltrating lymphocytes (TIL). Based on observations in human prostate adenocarcinomas and transitional cell carcinomas, we have investigated the presence of TIL in different stages of RCC in correlation to vascular endothelial growth factor (VEGF) expression as a parameter for tumor progression and adverse survival in RCC patients. Methods: Samples from surgically obtained RCC (n = 28) and benign renal parenchyma (n =10) were snap-frozen and processed by double-immunofluorescence staining with CD4/CD8 and VEGF antibodies. Results: In 20 of 28 RCCs a coexpression of TIL-specific markers CD4 and/or CD8 and VEGF was demonstrated. Control tissues were VEGF-negative and showed only negligible infiltration by CD4- or CD8-positive lymphocytes. Conclusion: The results indicate that at least 71% of TIL produce VEGF and may promote tumor progression rather than represent an abortive antitumor response of the host immune system.

Lysophosphatidic Acid (LPA)-Induced Vascular Endothelial Growth Factor (VEGF) by Mesothelial Cells and Quantification of Host-Derived VEGF in Malignant Ascites

“…In accordance, malignant ascites in ovarian or gastrointestinal cancer patients contains elevated levels of VEGF [8 -11]. Although VEGF in ascites has been considered to mainly originate from the tumor in most cases, various host cells such as macrophages [12], lymphocytes [13], neutrophils [14], and platelets [15], as well as fibroblasts [16] have also been shown to be capable of producing VEGF.…”

Komplementär- und Alternativmedizin in der Uro-Onkologie

“…Hierbei werden aus dem Tumor immunkompetente Zellen isoliert und den Patienten retransfundiert. Die prinzipielle Gefährlichkeit solcher Maßnahmen ist durch Charakterisierung der tumorinfiltrierenden Lymphozyten belegt worden [18]. Diesen Zellen wird a priori eine Abwehrfunktion im Rahmen des Tumorgeschehens zugeschrieben.…”

“…Diesen Zellen wird a priori eine Abwehrfunktion im Rahmen des Tumorgeschehens zugeschrieben. Untersuchungen an menschlichen Nierenzellkarzinompräparaten haben belegt, dass die tumorinfiltrierenden Lymphozyten nicht der Tumorabwehr dienen, sondern gefäßneubildende Substanzen (VEGF) produzieren [18]. Diese Substanzen bereiten dem Tumor eine Infrastruktur, die ideale Voraussetzungen für ein uneingeschränktes Tumorwachstum durch vaskuläre Versorgung gewährleistet [18].…”