BACKGROUND: Transitional cell carcinoma (TCC) of the bladder is associated with alterations in the immune system of the host. The authors demonstrated that in patients with bladder carcinoma there is a negative correlation between the levels of natural killer (NK) activity and the clinical evolution and pathologic stages of disease. METHODS: The authors investigated the effect of various doses of recombinant interferon-alpha-2b (IFN-alpha-2b) for variable periods of culture on the nonmajor histocompatibility-restricted cytotoxic activity of peripheral blood mononuclear cells (PBMNC) with or without CD16 and CD3-depleted populations from patients with superficial (confined to the mucosa or lamina propria) and infiltrative (those infiltrating beyond the lamina propria) TCC of the bladder using 4-hour 51-sodium chromate (51Cr)-release cytotoxicity assays against both NK-sensitive (K562) and NK-resistant (JY) tumor target cells. RESULTS: The normal NK activity detected in PBMNC from patients with superficial TCC of the bladder can be significantly enhanced by short-term (18-hour) incubation with recombinant IFN-alpha (P < 0.05). The depressed NK cytotoxic activity found in PBMNC from patients with infiltrative TCC can also be significantly enhanced, but not normalized, by short-term (18-hour) incubation with recombinant IFN-alpha (P < 0.05). Short-term recombinant IFN-alpha-incubated PBMNC from patients with superficial, but not infiltrative, TCC of the bladder also showed marked cytotoxic activity against NK-resistant target cells. By selection with CD16 or CD3 monoclonal antibodies and complement, it was also found that the precursor and effector lymphocytes of this recombinant IFN-alpha-promoted cytotoxicity belong to NK lineage. In kinetic studies, it was found that the maximal levels of the recombinant IFN-alpha-promoted cytotoxic activity against NK-sensitive and NK-resistant target cells in PBMNC from patients with TCC were reached after 18 hours of culture. CONCLUSION: Recombinant IFN-alpha can enhance the nonmajor histocompatibility-restricted cytotoxic activity of PBMNC from patients with TCC of the bladder.
BACKGROUND: Transitional cell carcinoma (TCC) of the bladder is associated with alterations in the immune system of the host. The authors demonstrated that in patients with bladder carcinoma there is a negative correlation between the levels of natural killer (NK) activity and the clinical evolution and pathologic stages of disease. METHODS: The authors investigated the effect of various doses of recombinant interferon-alpha-2b (IFN-alpha-2b) for variable periods of culture on the nonmajor histocompatibility-restricted cytotoxic activity of peripheral blood mononuclear cells (PBMNC) with or without CD16 and CD3-depleted populations from patients with superficial (confined to the mucosa or lamina propria) and infiltrative (those infiltrating beyond the lamina propria) TCC of the bladder using 4-hour 51-sodium chromate (51Cr)-release cytotoxicity assays against both NK-sensitive (K562) and NK-resistant (JY) tumor target cells. RESULTS: The normal NK activity detected in PBMNC from patients with superficial TCC of the bladder can be significantly enhanced by short-term (18-hour) incubation with recombinant IFN-alpha (P < 0.05). The depressed NK cytotoxic activity found in PBMNC from patients with infiltrative TCC can also be significantly enhanced, but not normalized, by short-term (18-hour) incubation with recombinant IFN-alpha (P < 0.05). Short-term recombinant IFN-alpha-incubated PBMNC from patients with superficial, but not infiltrative, TCC of the bladder also showed marked cytotoxic activity against NK-resistant target cells. By selection with CD16 or CD3 monoclonal antibodies and complement, it was also found that the precursor and effector lymphocytes of this recombinant IFN-alpha-promoted cytotoxicity belong to NK lineage. In kinetic studies, it was found that the maximal levels of the recombinant IFN-alpha-promoted cytotoxic activity against NK-sensitive and NK-resistant target cells in PBMNC from patients with TCC were reached after 18 hours of culture. CONCLUSION: Recombinant IFN-alpha can enhance the nonmajor histocompatibility-restricted cytotoxic activity of PBMNC from patients with TCC of the bladder.
Authors: Ahmad A Tarhini; Sandra J Lee; Xiaoxue Li; Uma N M Rao; Arun Nagarajan; Mark R Albertini; Jerry W Mitchell; Stuart J Wong; Mark A Taylor; Noel Laudi; Phu V Truong; Robert M Conry; John M Kirkwood Journal: Clin Cancer Res Date: 2018-11-12 Impact factor: 12.531
Authors: Ahmad A Tarhini; John Cherian; Stergios J Moschos; Hussein A Tawbi; Yongli Shuai; William E Gooding; Cindy Sander; John M Kirkwood Journal: J Clin Oncol Date: 2011-12-19 Impact factor: 44.544
Authors: M Alvarez-Mon; O J Salmerón; L Manzano; M Rodríguez-Zapata; E Reyes; L M Vaquer; J Carballido Journal: Med Oncol Date: 1995-03 Impact factor: 3.064
Authors: L Molto; M Alvarez-Mon; J Carballido; L Manzano; C Guillen; A Prieto; C Olivier; M Rodriguez-Zapata Journal: Br J Cancer Date: 1994-12 Impact factor: 7.640
Authors: Ahmad Tarhini; Yan Lin; Huang Lin; Zahra Rahman; Priyanka Vallabhaneni; Prateek Mendiratta; James F Pingpank; Matthew P Holtzman; Erik C Yusko; Julie A Rytlewski; Uma N M Rao; Robert L Ferris; John M Kirkwood Journal: J Immunother Cancer Date: 2018-10-23 Impact factor: 13.751