Monitoring of anti-tumour cell-mediated response in patients with renal cell carcinoma, disturbance of T cell proliferation
Authors:
Š. Lukešová 1,4; V. Vroblová 2; D. Hlávková 2; O. Kopecký 1,4; D. Vokurková 2; P. Morávek 3; H. Šafránek 3; P. Souček 2
Authors‘ workplace:
II. interní klinika Lékařské fakulty UK a FN Hradec Králové, přednosta. prof. MUDr. Jaroslav Malý, CSc.
1; Ústav klinické imunologie a alergologie Lékařské fakulty UK a FN Hradec Králové, přednosta prof. RNDr. Jan Krejsek, CSc.
2; Urologická klinika Lékařské fakulty UK a FN Hradec Králové, přednosta. doc. MUDr. Petr Morávek, CSc.
3; Oddělení klinické imunologie a mikrobiologie Oblastní nemocnice Náchod, přednosta prim. MUDr. Otakar Kopecký, CSc.
4
Published in:
Vnitř Lék 2008; 54(2): 139-145
Category:
Original Contributions
Overview
Introduction:
When checking tumour growth, a number of observations indicate that the immune system plays a significant role in patients with renal cell carcinoma (“RCC”). Infiltration by lymphocytes (tumour infiltrating lymphocytes, “TILs”) is more prevalent in RCC than any other tumours. T lymphocytes are the dominant population of TIL cells. Views concerning the role of T lymphocytic subpopulations, B lymphocytes and NK cells in an anti-tumour response are not established.
Aim:
The aim is to determine the phenotype and activation of lymphocytic cells and to compare their representation in tumour stroma (TIL), peripheral blood (PBL) and renal vein blood in patients with RCC.
Patients and methods:
The samples of peripheral blood taken from the cubital and renal veins and tumour stroma cells were obtained from 60 patients in the course of their surgeries carried out due to primary RCC. TILs were isolated from mechanically disintegrated tumour tissue. Immunophenotype multiparametric analysis of PBL and TILs was carried out. Their surface and activation characteristics were determined by means of flow cytometer.
Results:
CD3+ T lymphocytes (70.4 %) were the main population of TILs. The number of CD3+/CD8+ T lymphocytes was significantly higher in TILs, 39.7 % (p < 0.01), while CD4+ T lymphocytes were the majority population in peripheral blood, 41.35 % (p < 0.001). The representation of CD3+/69+ T lymphocytes was significantly higher in TILs, 32.05 %, compared to PBL (p < 0.001). On the contrary, the numbers of CD3+/CD25+, CD8+/57+ and CD4+/RA+ (naive CD4+ T lymphocytes) were higher in PBL (p < 0.001). The differences in representation of (CD3-/16+56+) NK cells and CD3+/DR+ T cells in TILs and PBL were not significant.
Conclusion:
The above-mentioned results prove that the characteristics and intensity of anti-tumour responses are different in compared compartments (tumour/PBL). CD3+/CD8+ T lymphocytes are the dominant lymphocytic population of TILs. The knowledge of phenotype and functions of effector cells, which are responsible for anti-tumour response, are the basic precondition for understanding the anti-tumour immune response and the cause of its failure.
Key words:
tumour-infiltrating lymphocytes - CD4 - CD8 - flow cytometry - renal cell carcinoma
Sources
1. Bayer AL, Baliga P, Woodward JE. Differential effects of transferrin receptor blockade on cellular mechanisms involved in graft rejection. Transplant Immunol 1999; 7: 131.
2. Bayer AL, Baliga P, Woodward JE. Transferrin receptor in T cell activation and transplantation. J Leukocyte Biol 1998; 64: 19.
3. Bilik R, Mor C, Hazaz B et al. Characterisation of T lymphocyte populations infiltrating primary breast cancer. Cancer Immunol. Immunother 1989; 28: 143-147.
4. Böhm M, Ittenson A, Schierbaum KF et al. Pretreatment with interleukin-2 modulates peri-operative immuno-dysfunction in patients with renal cell carcinoma. Eur Urol 2002; 41: 458-468.
5. Bremers AJA, Parmiani G. Immunology and immunotherapy of human cancer: present concepts and clinical developments. Crit Rev Oncol Hematol 2000; 34: 1-25.
6. Bubeník J. Interleukin-2 Therapy of Cancer. Folia Biol (Praha) 2004; 50: 120-130.
7. Coventry BJ, Weeks SC, Heckford SE et al. Lack of IL-2 cytokine expression despite IL-2 messenger RNA transcription in tumor-infiltrating lymphocytes in primary human breast carcinoma: selective expression of early activation markers. J Immunol 1996; 156: 3486.
8. Chadburn A, Inghirami G, Knowels DM. The kinetics and temporal expression of T cell activation-associated antigens CD15 (LeuM1), CD30 (Ki-1) EMA and CD11c (LeuM5) by benign activated T cells. Hematol Pathol 1992; 6: 193.
9. Chakraborty NG, Sporn JR, Pasquale DR et al. Suppression of lymphokine-activated killer cell generation by tumor-infiltrating lymphocytes. Clin Immunol Immunopathol 1991; 59: 407-416.
10. Characiejus D, Pašukoniené V, Kazlauskaité N et al. Predictive value of CD8highCD57+ lymphocyte subset in interferon therapy of patients with renal cell carcinoma. Anticancer Res 2002; 22: 3679-3684.
11. de Jong EC, Smits HH, Kapsenberg ML. Dendritic cell-mediated T cell polarization. Spr Sem Immun 2005; 26: 289-307.
12. Donskov F, Bennedsgaard KM, von der Maase H et al. Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival. Br J Cancer 2002; 87: 194-201.
13. Eckschlager T, Kodet R. Renal cell carcinoma in children: a single institution’s experience. Med Pediatr Oncol 1994; 23: 36-39.
14. Elsässer-Beile U, Gierschner D, Welchner T et al. Different expression of Fas and Fas ligand in tumor infiltrating and peripheral lymphocytes of patients with renal cell carcinomas. Anticancer Res 2003; 23: 433-438.
15. Elsässer-Beile U, Grussenmeyer T, Gierschner D et al. Semiquantitative analysis of Th1 and Th2 cytokine expression in CD3+, CD4+, and CD8+ renal-cell-carcinoma-infiltrating lymphocytes. Cancer Immunol. Immunother 1999; 48: 204-208.
16. Hayakawa K, Morita T, Augustus LB et al. Human renal cell carcinoma cells are able to activate natural killer cells. Int J Cancer 1992; 51: 290.
17. Igarashi T, Takahashi H, Tobe T et al. Effect of tumor-infiltrating lymphocyte subsets on prognosis and susceptibility to interferon therapy in patients with renal cell carcinoma. Urol Int 2002; 69: 51-56.
18. Indrová M, Bubeník J, Jakoubková J et al. Subcutaneous interleukin-2 in combination with vinblastine for metastatic renal cancer: cytolytic activity of peripheral blood lymphocytes. Neoplasma 1994; 41: 197-200.
19. Klener P jr, Anděra L, Klener P et al. Cell death signalling pathway in the pathogenesis and therapy of haematologic malignancies: Overview of therapeutic approaches. Folia Biol (Praha) 2006; 52: 119-136.
20. Koo AS, Tso CL, Shimabukuro T et al. Autologous tumor-specific cytotoxicity of tumor-infiltrating lymphocytes derived from human renal cell carcinoma. J Immunother 1991; 10: 347-354.
21. Kowalczyk D, Skorupski W, Kwias Z et al. Flow cytometric analysis of tumour-infiltrating lymphocytes in patients with renal cell carcinoma. Br J Urol 1997; 80: 543-547.
22. Kronke M, Leonard WJ, Depper JM et al. Sequential expression of genes involved in human T lymphocyte growth and differentiation. J Exp Med 1985; 161: 1593-1598.
23. Lucivero G, Dalla Mora L, Bresciano E et al. Functional characteristics of cord blood T lymphocytes after lectin and anti-CD3 stimulation. Differences in the way T cells express activation molecules and proliferate. Int J Clin Res 1996; 26: 255.
24. Lukešová Š, Kopecký O, Vroblová V et al. Porovnání v zastoupení lymfocytárních populací u světlobuněčného karcinomu ledviny (v nádorové tkáni, renální žíle a periferní krvi). 307-309. In: Edukační sborník z XXX. brněnských onkologických dnů s XX. Konferencí pro sestry a laboranty. Brno: Masarykův onkologický ústav 2006.
25. Malinowski K, Kono K, Takayama T et al. Inhibition of lymphocyte proliferative responses by renal cell carcinoma extract. Transplant Proc 1997; 29: 839.
26. Martel CL, Lara PN Renal cell carcinoma: current status and future directions. Crit Rev Oncol Hematol 2003; 45: 177-190.
27. Mitropoulos D, Kooi S, Rodriguez-Villanueva J et al. Characterization of fresh (uncultured) tumour-infiltrating lymphocytes (TIL) and TIL-derivied T cell lines from patients with renal cell carcinoma. Clin Exp Immunol 1994; 97: 321-327.
28. Nakamura K, Kitani A, Fuss I et al. TGF-β1 plays an important role in the mechanism of CD4+ CD25– regulatory T cell activity in both humans and mice. J Immunol 2004; 172: 834-842.
29. Panelli MC, Nagorsen D, Wang E et al. Mechanism of immune response during immunotherapy. Yonsei Med J 2004; 45 (Suppl): 15-17.
30. Park H, Paik D, Jang E et al. Acquisition of anergic and suppressive activities in transforming growth factor-β-costimulated CD4+ CD25– T cells. Inter Immunol 2004; 16: 1203-1213.
31. Reed JC, Alpers JD, Nowell PC et al. Sequential expression of protooncogenes during lecitin-stimulated mitogenesis of normal human lymphocytes. Proc Natl Acad Sci USA 1986; 83: 3982-3986.
32. Rodriguez MA, De Sanctis JB, Blasini AM et al. Human IFN-γ up-regulates IL-2 receptors in mitogen-activated T lymphocytes. Immunol 1990; 69: 554.
33. Santin AD, Ravaggi A, Bellone S et al. Tumor-infiltrating lymphocytes contain higher numbers of type 1 cytokine expressors and DR+ T cells compared with lymphocytes from tumor draining lymph nodes and peripheral blood in patients with cancer of the uterine cervix. Gynecol Oncol 2001; 81: 424-432.
34. Shabtai M, Ye H, Frischer Z et al. Increased expression of activation markers in renal cell carcinoma infiltrating lymphocytes. J Urol 2002; 168: 2216-2219.
35. Schoof DD, Terashima Y, Peoples GE et al. CD4+ T cell clones isolated from human renal cell carcinoma possess the functional characteristics of Th2 helper cells. Cellular Immunol 1993; 150: 114-123.
36. Tiemessen MM, Kunzmann S, Schmidt-Weber CB et al.: Transforming growth factor-β inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response. Inter Immunol 2003; 12: 1495-1504.
37. van den Hove LE, van Gool SW, van Poppel H et al. Identification of an enriched CD4+ CD8α++ CD8β+ T-cell subset among tumor-infiltrating lymphocytes in human renal cell carcinoma. Int J Cancer 1997; 71: 178.
38. van den Hove LE, van Gool SW, van Poppel H et al. Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating lymphocytes in human renal cell carcinoma. Clin Exp Immunol 1997; 109: 501-509.
39. Whiteside TL, Herberman RB The role of natural killer cells in immune surveillance of cancer. Curr Opinion Immunol 1995; 7: 704-710.
40. Whitford P, Mallon EA, George WD et al. Flow cytometric analysis of tumour infiltrating lymphocytes in breast cancer. Br J Cancer 1990; 62: 971-975.
41. Zeromski J, Dworacki G, Kruk-Zagajewska A et al. Assessment of immunophenotype of potentially cytotoxic tumor infiltrating cells in laryngeal carcinoma. Arch Immunol Ther Exp 1993; 41: 57-62.
Labels
Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
2008 Issue 2
Most read in this issue
- Peripheral arterial disease of extremities – guidelines for diagnostic and treatment
- Monitoring of anti-tumour cell-mediated response in patients with renal cell carcinoma, disturbance of T cell proliferation
- The scintigraphic 99mTc-MAA imaging quantification of the right-to-left shunt in a patients with multiple pulmonary arteriovenous malformation and familial teleangiectasis
- Current Use of Magnetic Resonance Imaging in Cardiology