Molecular mechanisms of T cell recruitment into renal cell carcinoma
Year: 2008
Session type: Poster / e-Poster / Silent Theatre session
1Institute for Cancer Studies, University of Birmingham, Birmingham, UK, 2Institute of Biomedical Research, University of Birmingham, Birmingham, UK, 3Department of Urology, Queen Elizabeth Hospital, Birmingham, UK, 4Department of Pathology, Queen Elizabeth Hospital, Birmingham, UK
Abstract
Background
Treating cancer with tumour-specific T cells can yield clinical responses in some patients. However, this approach frequently fails, possibly due to inefficient homing of effector T cells to the tumour tissue or immune evasion mechanisms at the tumour site (e.g. presence of Tregs). T cell infiltration of tissues is orchestrated by a variety of ligand and receptor molecules expressed both on the T cell surface and the target tissue. To aid further development of T cell therapy for renal cell carcinoma (RCC) we are investigating the mechanisms whereby T cells are naturally recruited to this tumour.
Method
During the first stage of the project flow cytometric analysis of 23 RCC samples determined the homing phenotype of tumour infiltrating lymphocytes (TIL).
Results and conclusion
Both CD4+ and CD8+ T cells present in tumour tissue showed expression of chemokine receptors CCR1, CCR2, CCR5, CXCR3, CXCR4, CXCR6 and CX3CR1, and adhesion molecules CD62L, LFA-1, PSGL-1 and VLA4. Interestingly a third of samples contained a significant number (>5% of CD3+ TIL) of double positive CD4+CD8+ T cells, which carried a similar homing phenotype. Our preliminary data suggest ~5% of TIL are Foxp3+ Tregs, and we are currently assessing their homing phenotype. To look for evidence of selective recruitment through specific homing markers results with TIL will be compared with memory and regulatory T cell populations in matched peripheral blood and normal kidney tissue. Having identified homing markers of interest, we aim to test their function and explore the tissue distribution of their ligands.
Background
Treating cancer with tumour-specific T cells can yield clinical responses in some patients. However, this approach frequently fails, possibly due to inefficient homing of effector T cells to the tumour tissue or immune evasion mechanisms at the tumour site (e.g. presence of Tregs). T cell infiltration of tissues is orchestrated by a variety of ligand and receptor molecules expressed both on the T cell surface and the target tissue. To aid further development of T cell therapy for renal cell carcinoma (RCC) we are investigating the mechanisms whereby T cells are naturally recruited to this tumour.
Method
During the first stage of the project flow cytometric analysis of 23 RCC samples determined the homing phenotype of tumour infiltrating lymphocytes (TIL).
Results and conclusion
Both CD4+ and CD8+ T cells present in tumour tissue showed expression of chemokine receptors CCR1, CCR2, CCR5, CXCR3, CXCR4, CXCR6 and CX3CR1, and adhesion molecules CD62L, LFA-1, PSGL-1 and VLA4. Interestingly a third of samples contained a significant number (>5% of CD3+ TIL) of double positive CD4+CD8+ T cells, which carried a similar homing phenotype. Our preliminary data suggest ~5% of TIL are Foxp3+ Tregs, and we are currently assessing their homing phenotype. To look for evidence of selective recruitment through specific homing markers results with TIL will be compared with memory and regulatory T cell populations in matched peripheral blood and normal kidney tissue. Having identified homing markers of interest, we aim to test their function and explore the tissue distribution of their ligands.
