Cellular Immunity and Renal Cell Cancer
Study Details
Study Description
Brief Summary
Renal cell cancer (RCC) is one of the most important urogenital tumors because of it's high mortality and increasing incidence. RCC, which accounts about 3% of all malignant tumors in the adults, is the most lethal urogenital cancer. The high mortality rate stimulate investigator groups to study RCC pathogenesis including immunological part. It is interesting that immunotherapy was firstly started in patients with metastatic RCC using IL-2 and interferon gamma. The first results were promising but the exact mechanism of acting was not found. In the RCC, as in the others tumors, immune cells (T lymphocytes, NK and NKT cells) are responsible for main antitumor effect. Their effect was caused by cytotoxic activity on the tumor cells. In the investigation investigators will determine patterns of aggregation of tumor infiltrating immune cells in the blood, healthy kidney and carcinomatous tissue. But, presence of this cells not implicated that this cells are active. Their activity will be determined by proofing cytotoxicity of different subgroup of immune cells. In that way investigators will present different patterns of aggregation of tumor infiltrating immune cells and their cytotoxicity which will direct that this cells are active with antitumor effect. Correlation of collected data with classical prognostic factors in the patients with RCC as tumor staging, tumor grading (Fuhrman) and histological subtype will help to determine some immunological factors as possible new prognostic factors. For conclusion, the results of this study will allow better understanding of RCC pathogenesis, specially their immunological part and become a foundation for the future investigations.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Cellular immunity will be investigated in the two group of patients: operated patients with RCC and healthy volunteers.
In the study investigators will determine patterns of aggregation of tumor infiltrating immune cells in the blood (RCC patients and volunteers), healthy kidney and carcinomatous tissue as their cytotoxicity (only RCC patients).
Investigators will determine:
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presence of different immune cells in the blood and kidney tissue (T lymphocytes, NK cells, NKT cells, T regulatory cells),
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presence and distribution of cytolytic molecule perforin and granulysin in immune cells (T lymphocytes, NK cells, NKT cells) in the blood, kidney tissue and urine
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NK cytotoxicity
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possible correlation between presence of immune cells and clinical prognostic factors
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| RCC patients RCC patients (30 pts) will include patients with kidney cancer (renal cell cancer). Investigators will collect and analyze: blood sample, urine sample, kidney tissue sample (healthy tissue, carcinomatous tissue and borderline tissue between them). |
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| Healthy patients In this group (30 patients) will be recruiting healthy patients (volunteer). Investigators will collect and analyze: blood sample. |
Outcome Measures
Primary Outcome Measures
- Distribution of immune cells between two groups measured in the blood samples [7 months]
Determination of distribution of immune cells between two groups in their blood samples with their comparison.
- Distribution of immune cells between different tissue samples (RCC vs. healthy tissue vs. borderline tissue) [7 months]
Determination of distribution of immune cells between different tissue samples with their comparison
- Determination of NK cytotoxicity [7 months]
Determination of NK cytotoxicity
Eligibility Criteria
Criteria
Inclusion Criteria:
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RCC (renal cell cancer) patients
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operated patients
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both gender
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older than 18 years
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written informed consent
Exclusion Criteria:
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age younger of 18
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patients with metastatic disease
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patients receiving antibiotics 6 weeks before operation
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patients regularly treated with corticosteroids or immunosuppressive drugs
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transplanted patients
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patients with autoimmune diseases and/or vasculitis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Hospital Center Rijeka | Rijeka | Croatia | 51 000 |
Sponsors and Collaborators
- Clinical Hospital Center Rijeka
Investigators
- Principal Investigator: Dean Markić, MD, PhD, Clinical Hospital Center Rijeka
Study Documents (Full-Text)
None provided.More Information
Publications
- Cózar JM, Canton J, Tallada M, Concha A, Cabrera T, Garrido F, Ruiz-Cabello Osuna F. Analysis of NK cells and chemokine receptors in tumor infiltrating CD4 T lymphocytes in human renal carcinomas. Cancer Immunol Immunother. 2005 Sep;54(9):858-66. Epub 2005 May 11.
- Finke JH, Tubbs R, Connelly B, Pontes E, Montie J. Tumor-infiltrating lymphocytes in patients with renal-cell carcinoma. Ann N Y Acad Sci. 1988;532:387-94.
- Mrakovcić-Sutić I, Bacić D, Golubović S, Bacić R, Marinović M. Cross-talk between NKT and regulatory T cells (Tregs) in modulation of immune response in patients with colorectal cancer following different pain management techniques. Coll Antropol. 2011 Sep;35 Suppl 2:57-60.
- Oldham KA, Parsonage G, Bhatt RI, Wallace DM, Deshmukh N, Chaudhri S, Adams DH, Lee SP. T lymphocyte recruitment into renal cell carcinoma tissue: a role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6. Eur Urol. 2012 Feb;61(2):385-94. doi: 10.1016/j.eururo.2011.10.035. Epub 2011 Nov 4.
- Shabtai M, Ye H, Frischer Z, Martin J, Waltzer WC, Malinowski K. Increased expression of activation markers in renal cell carcinoma infiltrating lymphocytes. J Urol. 2002 Nov;168(5):2216-9.
- Sotosek S, Sotosek Tokmadzic V, Mrakovcic-Sutic I, Tomas MI, Dominovic M, Tulic V, Sutic I, Maricic A, Sokolic J, Sustic A. Comparative study of frequency of different lymphocytes subpopulation in peripheral blood of patients with prostate cancer and benign prostatic hyperplasia. Wien Klin Wochenschr. 2011 Dec;123(23-24):718-25. doi: 10.1007/s00508-011-0096-7. Epub 2011 Nov 23.
- Sotosek Tokmadzic V, Laskarin G, Mahmutefendic H, Lucin P, Mrakovcic-Sutic I, Zupan Z, Sustic A. Expression of cytolytic protein-perforin in peripheral blood lymphocytes in severe traumatic brain injured patients. Injury. 2012 May;43(5):624-31. doi: 10.1016/j.injury.2010.05.009. Epub 2010 May 26.
- Xia Y, Zhang Q, Zhen Q, Zhao Y, Liu N, Li T, Hao Y, Zhang Y, Luo C, Wu X. Negative regulation of tumor-infiltrating NK cell in clear cell renal cell carcinoma patients through the exosomal pathway. Oncotarget. 2017 Jun 6;8(23):37783-37795. doi: 10.18632/oncotarget.16354.
- Zhang Q, Jia Q, Deng T, Song B, Li L. Heterogeneous expansion of CD4+ tumor-infiltrating T-lymphocytes in clear cell renal cell carcinomas. Biochem Biophys Res Commun. 2015 Feb 27;458(1):70-6. doi: 10.1016/j.bbrc.2015.01.069. Epub 2015 Jan 28.
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