Relationship between responsiveness of cancer cells to Oncostatin M and/or IL-6 and survival of stage III melanoma patients treated with tumour-infiltrating lymphocytes

• Published in: The Journal of pathology Vol. 216; no. 4; pp. 451 - 459
• Main Authors: Lacreusette, A, Lartigue, A, Nguyen, J.M, Barbieux, I, Pandolfino, M.C, Paris, F, Khammari, A, Dréno, B, Jacques, Y, Blanchard, F, Godard, A
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.12.2008; Wiley
• Subjects: Adoptive Transfer - methods; Animals; Biological and medical sciences; Blotting, Western - methods; Cell Line, Tumor; Cell Proliferation - drug effects; Dermatology; Disease-Free Survival; Follow-Up Studies; Humans; interleukin-6; Interleukin-6 - metabolism; Interleukin-6 - secretion; Interleukin-6 - therapeutic use; Investigative techniques, diagnostic techniques (general aspects); lymph nodes; Lymphatic Metastasis; Lymphocytes, Tumor-Infiltrating - secretion; Lymphocytes, Tumor-Infiltrating - transplantation; Medical sciences; Melanoma - drug therapy; Melanoma - pathology; Melanoma - therapy; melanoma xenograft tumours in nude mice; Mice; Mice, Nude; Neoplasm Staging; Oncostatin M; Oncostatin M - secretion; Oncostatin M - therapeutic use; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Receptors, Interleukin-6 - metabolism; Receptors, Oncostatin M - metabolism; Retrospective Studies; retrospective study of relapse-free survival; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Skin Neoplasms - therapy; stage III human melanoma; Tumors of the skin and soft tissue. Premalignant lesions; tumour-infiltrating lymphocytes; Xenograft Model Antitumor Assays; Relapse free survival; melanoma xenograft tumours in nude mice; tumour-infiltrating lymphocytes; Heterograft; Heterotransplantation; interleukin-6; Interleukin 6; retrospective study of relapse-free survival; Malignant melanoma; Advanced stage; Tumor cell; Human; Lymph node; Cytokine; Rodentia; stage III human melanoma; Tumor infiltrating lymphocyte; Malignant tumor; Oncostatin M; Retrospective; Vertebrata; Anatomic pathology; Mammalia; Treatment; Mouse; lymph nodes; Animal; Locally advanced stage; Cancer
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2416

Immunotherapy by adoptive transfer of autologous tumour-infiltrating lymphocytes (TIL) shows promising clinical results for stage III (lymph nodes metastasis) melanoma patients, but some of them remain unresponsive. Here we analysed retrospectively the impact of resistance of melanoma cells to anti-proliferative cytokines on the clinical outcome of 24 TIL-treated metastatic melanoma patients. Patient relapse-free survival correlated significantly with Oncostatin M (OSM) and/or IL-6 sensitivity of melanoma cells, but not with interferon (IFN) γ or tumour necrosis factor (TNF) α sensitivity. However, OSM/IL-6 sensitivity did not correlate with other known prognostic factors. Moreover, OSM and IL-6 were produced by TIL just before their injection to patients. In immunodeficient mice, OSM reduced human melanoma xenograft tumour growth, this effect being directly through inhibition of tumour cell proliferation rather than induction of apoptosis or necrosis. Thus, OSM/IL-6 resistance of melanoma cells appears to be a new escape mechanism to TIL treatment that could be added to the existing prognostic factors for early stage melanoma patients. This mechanism of action could be also relevant in other immunotherapy protocols, and could lead to better prognosis and anti-cancer treatments. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.