44P - Role of functional determinants of Th17 & Treg cells in immune evasion of urothelial carcinoma of bladder

Date 20 November 2015
Event ESMO Symposium on Immuno-Oncology 2015
Session Welcome reception and general Poster viewing
Topics Urothelial Cancers
Cancer Immunology and Immunotherapy
Presenter Alpana Sharma
Citation Annals of Oncology (2015) 26 (suppl_8): 5-14. 10.1093/annonc/mdv514
Authors A. Sharma1, V. Anand1, A. Sharma2, A. Seth3, M. Sharma4
  • 1Department Of Biochemistry, All India Institute of Medical Sciences, 110029 - New Delhi/IN
  • 2Department Of Medicine, Jawaharlal Nehru Medical College, Aligarh, Uttar Pradesh, Aligarh/IN
  • 3Department Of Urology, All India Institute of Medical Sciences, New Delhi/IN
  • 4Department Of Radiation Oncology, Maulana Azad Medical College New Delhi A.L.N. Hospital, New Delhi/IN

Abstract

Aim

UBC (Urothelial Carcinoma of bladder) is large term for malignancy of the bladder affecting different types of cells and to various different extents. There are several notable immunological development associated with the physiological changes in tumor microenvironment as a result of tumour development. Th17 and Treg (T-regulatory) axis, which have been found to be involved in many inflammatory disorders might also immunomodulate the microenvironment of Bladder cancer which can be potential novel therapeutic target.

Methods

In this study, 35 UBC patients and 30 healthy individuals have been registered to determine the circulatory level of Th17 (IL17, IL23 and IL22) and Treg (TGFß) related cytokines. Frequency of Th17 and Treg cells in circulation has been observed by FACs. Quantitative molecular expression of IL17, RORɣT (Th17 transcription factor), TGFß and FOXP3 (Treg transcription factor) has also been observed in the tissue of UBC patients.

Results

Significant increase (p < 0.001) in the circulatory level of IL17, IL23, IL22 and TGFß has been observed as compared to controls. Frequency of Th17 cells were found to be significantly higher (p < 0.001) in UBC patients as compared to controls. Whereas, the frequency distribution of Treg cells in UBC patients was found to be lowered which was statistically insignificant (p < 0.113). Q-PCR showed significantly higher expression (p < 0.001) of IL17, RORɣT and TGFß in tumor tissue as compared to adjacent non-tumor tissue. Expression of FOXP3 was significantly decreased in tumor tissue as compared to adjacent non-tumor tissue.

Conclusions

These finding indicates that there is potential involvement of Th17 cells in UBC as compared to Treg cells. The increased circulatory levels of IL17, IL23 and IL22 (Th17 related cytokines) and molecular expression of IL17 and RORɣT in bladder cancer patients might suggest the prominent role of these molecules in differentiation and proliferation of Th17 cells in this disease. Higher level of TGFß might indicate the involvement of other immune cells in the inflammatory response of UBC. Further study in larger patient cohort might be an aide to formulate an efficient therapeutic strategy with Th17 as a target in UBC.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.