A New Approach in the Management of Urothelial Tumors Using GM-CSF on Marker Lesions: An Ultrastructural and Immunohistochemical Study on the Macrophage Population in Bladder Mucosa

Abstract

Our purpose was to investigate a new therapeutic model, GM-CSF-targeted immunomodulation on transitional cell carcinoma (TCC) marker lesions and to evaluate the immunologic response of the bladder mucosa. Eleven patients with pTa or pT1 bladder cancer were eligible for the study. All lesions were removed by transurethral resection (TUR) except for a marker lesion. All patients received 8 weekly instillations of 300 microg of GM-CSF, after which cystoscopy with bladder biopsies +/- TUR was repeated on adjacent urothelium or tumor or both. Paraffin-embedded sections were immunohistochemically stained with CD68, which labels monocytes and macrophages. The CD68+ cell population was evaluated as 1+ to 3+. Comparable specimens were routinely processed for ultrastructural analysis. Complete response was observed in 6 patients (55%), persistent tumor occurred in 4 patients (approximately 36.4%), and 1 patient (8.6%) showed recurrence. Immunohistochemically, an at least twofold increase in the number of the CD68+ cells was observed in all responders. Submicroscopically, migration of macrophages to the surface layer occurred. Macrophages showed an extensive lysosomal system and pseudopodia. This study indicates that the prophylactic treatment of TCC with GM-CSF may induce immunomodulatory effects on macrophage activities, which could be associated with the clinical evolution of the disease.

Lymphocyte activation by granulocyte macrophage‐colony stimulating factor in human bladder cancer

“…There is abundant evidence suggesting that lymphocytes play a central role in the host response to tumor (12). Nonspecific phagocytes, i.e., macrophages, may also be involved, as it has already been shown (12,13). The treatment caused complete disappearance of the marker lesion in 55% of pts indicating that it is an effective treatment.…”

“…There is abundant evidence suggesting that lymphocytes play a central role in the host response to tumor (12). Nonspecific phagocytes, i.e., macrophages, may also be involved, as it has already been shown (12,13).…”

Th1 Cytokine-Secreting Recombinant Bacillus Calmette-Guérin: Prospective Use in Immunotherapy of Bladder Cancer

“…Other studies also supported the safety and antitumor activity of intravesical rIFN-γ monotherapy (Stavropoulos et al, 2002). Studies also demonstrated that intravesical rGM-CSF was effective as a prophylactic therapy for patients with NMIBC after TURBT (Stravoravdi et al, 1999;Theano et al, 2002). In correlation with regression of marker lesions, intravesical rGM-CSF induced leukocyte migration and activation in the bladder mucosa.…”

Th1 Cytokine-Secreting RecombinantMycobacterium bovisBacillus Calmette-Guérin and Prospective Use in Immunotherapy of Bladder Cancer

“…Other studies also supported the safety and antitumor activity of intravesical rIFN- γ monotherapy [72]. Studies also demonstrated that intravesical rGM-CSF was effective as a prophylactic therapy for patients with NMIBC after TURBT [73, 74]. In correlation with regression of marker lesions, intravesical rGM-CSF induced leukocyte migration and activation in the bladder mucosa.…”