Gains and losses of CD8, CD20 and CD56 expression in tumor stroma-infiltrating lymphocytes compared with tumor-associated lymphocytes from ascitic fluid and lymphocytes from tumor draining lymph nodes in serous papillary ovarian carcinoma patients

Serous papillary ovarian cancer (SPC) is a highly aggressive tumor. About two-thirds of women have advanced disease at the time of diagnosis. Although many women with disseminated disease respond at first to combinations of surgery and chemotherapy, nearly 90% of tumors recur and women die of disease. Update progress in our knowledge of tumor-associated antigens and insight into mechanisms involved in immune-mediated recognition of these antigens, have provided a strong starting point for using the immune system as a model for novel therapy. In this study we determined the immunological profile of tumor-infiltrating lymphocytes (TILs), tumor-associated lymphocytes (TALs) in ascitic fluids, and lymphocytes from tumor draining regional lymph nodes (LNs) in SPC patients by CD20 (L26), CD8, and CD56 immunostaining. We examined 14 cases of TILs, 15 cases of TALs and 19 cases of LNs. TILs were infiltrating tumor stroma. No significant difference was detected in TILs, TALs and LNs in the expression of the B-cell marker CD20. In contrast, CD8 (T-cytotoxic) and CD56 (natural killer cell, NK) markers were dominant in LNs and TALs, but not in TILs. We conclude that SPC tumor lymphocytic infiltrate demonstrates a deplete T cytotoxic (CD8+) and NK cell (CD56+) immunophenotypic profile. This might in part explain the poor clinical outcome of the disease.

Serous papillary ovarian carcinoma; Ascitic fluid; Tumor infiltrating lymphocytes; Tumor associated lymphocytes; Tumor draining lymph nodes; CDS, CD20, CD56

[1] Piver M. S., Baker T. P., Piedmonte M., Sandecki A. M.: "Epidemiology and etiology of ovarian cancer". Semin. Oneal., 1991, 18, 177.

[2] Rose P. G., Piver M. S., Tsukada Y., Lau T. S.: "Metastatic patterns in histologic variants of ovarian cancer: an autopsy study". Cancer, 1989, 64, 1508.

[3] Eifel P., Hendickson M., Ross J., Ballon S., Martinez A., Kempson R.: "Simultaneous presentation of carcinoma involving the ovary and the uterine corpus". Cancer, 1982, 50, 163.

[4] Kaminski P. F., Norris H. J.: "Coexistence of ovarian neoplasms and endocervical adenocarcinoma". Obst et. Gynecol., 1984, 64, 553.

[5] Rosai J.: "Female reproductive system (ovary). Ackerman's Textbook of Surgical Pathology", 8•h ed., St Louis, Mosby, 1996, 1461.

[6] Blaustein A.: "Peritoneal mesothelium and ovarian surface cells: shared characteristics". Int. J. Gynecol. Pathol., 1981, 3, 361.

[7] Foyle A., Al-Jabi M., McGaughey W. T. E.: "Papillary peritoneal tumors in women". Am. J. Surg. Pathol., 1981, 5, 241.

[8] Wick M. R., Mills S. E., Dehner L. P., Bollinger D. J., Fechner R E.: "Serous papillary carcinomas arising from peritoneum and the ovaries: clinicopathologic and immunohistochemical comparison". Int. J. Gynecol. Pathol., 1989, 8, 179.

[9] Rao B. R., Slotman B. J.: "Endocrine factors in common epithelial ovarian cancer". Endocr. Rev., 1991, 12, 14.

[10] Singer N. G., Todd R. F., Fox D. A.: "Structures on the cell surface. Update from fifth International Workshop on human leucocyte differentiation antigens". Arthritis and Rheumatism, 1994, 37, 1245.

[11] Santin A. D., Hermonat P. L., Ravaggi A., Bellone S., Roman J. J., Smith C. V., et al.: "Phenotypic and functional analysis of tumorinfiltrating lymphocytes compared with tumor-associated lymphocytes from ascitic fluid and peripheral blood lymphocytes in patients with advanced ovarian cancer". Gynecol. Obstet. Invest., 2001, 51 (4), 254.

[12] Santin A. D., Ravaggi A., Bellone S., Pecorelli S., Cannon M. J., Parham G. P., Hermonat P. L.: "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 (3), 424.

[13] Santin A. D., Bellone S., Ravaggi A., Pecorelli S., Cannon M. J., Parham G. P.: "Induction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells". Obstet. Gynecol., 2000, 96 (3), 422.

[14] Santin A. D., Hermonat P. L., Ravaggi A., Bellone S., Cowan C., Korourian S., et al.: "Development, characterization and distribution of adoptively transferred peripheral blood lymphocytes pnmed by human papillomavirus 18E7-pulsed autologous dendntic cells in a patient with metastatic adenocarcinoma of the uterine cervix". Eur. J. Gynaecol. Oneal., 2000, 21 (1), 17.

[15] Baxevanis C. N., Voutsas L F., Tsitsilonis 0. E., Gritzapis A. D., Sotiriadou R., Papamichail M.: "Tumor-specific CD4+ T lymphocytes from cancer patients are required for optimal induction of cytotoxic T cells against the autologous tumor". J Immunol., 2000, 164 (4), 3902.

[16] Santin A. D., Bellone S., Ravaggi A., Roman J. J., Pecorelli S., Parham G. P., Cannon M. J.: "Induction of tumour-specific CD8(+) cytotoxic T lymphocytes by tumour lysate-pulsed autol ogous dendritic cells in patients with uterine serous papillary cancer". Br. J. Cancer, 2002, 86 (1), 151.

[17] Baxevanis C. N., Dedoussis G. V Z., Papadopoulos N. G., Missitzis L, Stathopoulos G. P., Papamichail M.: "Tumor spec币c cytolysis by tumor infiltrating lymphocytes in breast cancer". Cancer, 1994, 74, 1275.

[18] Baxevanis C. N. G., Dedoussis V Z., Gritzapis A. D., Stathopoulos G. P., Papamichail M.: "Interleukin-I synergizes with interleukin-2 in the outgrowth of autologous tumor-reactive CDS+ effectors". Br. J. Cancer, 1994, 70, 625.

[19] Baxevanis C. N., Papamichail M.: "Characterization of the antitumor immune response in human cancers and strategies for immunotherapy''. Crit. Rev. Oneal. Hematol., 1994, 16, 157.

[20] Baxevanis C. N., Dedoussis G. V Z., Papadopoulos N. G., Missitzis L, Beroukas C., Stathopoulos G. P., Papamichail M.: "Enhanced human lymphokine-activated killer cell function after brief exposure to granulocyte-macrophage-colony stimulating factor" Cancer, 1995, 76, 1253.

[21] Baxevanis C. N., Tsiatas M. L., Cacoullos N. T., Spanakos G., Liacos C., Missitzis L, et al.: "Induction of anti-tumor lymphocytes in cancer patients after brief exposure to supernatants from cultures of anti-CD3-stimulated allogeneic lymphocytes". Br. J. Cancer, 1997, 76, 1072.

[22] Li Y., Bendandi M., Deng Y., Dunbar C., Munshi N., Jagannath S., et al.: "Tumor-specific recognition of human myeloma cells by idiotype-induced CDS+ T cells". Blood, 2000, 96, 2828.

[23] Santin A. D., Hermonat P. L., Ravaggi A., Chiriva-Internati M., Zhan D., Pecorelli S., et al.: "Induction of human papillomavirus-specific CD4+ and CD8+ lymphocytes by E7 pulsed autologous dendritic cells in patients with HPV 16 and 18 positive cervical cancer". J. Viral., 1999, 73, 5402.

[24] Nazaruk R., Rochford M. V,. Hobbs and M. J. Cannon: "Functional diversity of the CD8+ T cell response to Epstein-Barr virus (EBY): Implications for the pathogenesis of EBY-associated lymphoproliferative disorders". Blood, 1998, 91, 3875.