Melanoma: Dréno B

Saiag P, Bosquet L, Guillot B, Verola O, Avril MF, Bailly C, Cupissol D, Dalac S, Danino A, Dréno B, Grob JJ, Leccia MT, Renaud-Vilmer C, Négrier S, Anonymous00110. · Hôpital Ambroise Paré, 92104 Boulogne, Université Versailles-Saint Quentin, France. · Eur J Dermatol. · Pubmed #17540641 links to  free full text

This publication has no abstract.

Hauschild A, Gogas H, Tarhini A, Middleton MR, Testori A, Dréno B, Kirkwood JM. · Department of Dermatology, University of Kiel, Kiel, Germany. · Cancer. · Pubmed #18236459 links to  free full text

Abstract: Interferon-alpha-2b (IFNalpha2b) is the only effective adjuvant therapy for melanoma patients at high risk of recurrence that has been approved by regulatory authorities worldwide. However, IFN toxicities increase the risk of poor treatment compliance and impair the potential for benefit from this agent. A review of the literature demonstrated little recent attention to supportive care in the management of IFN toxicities. An international group of experts with extensive personal experience in the use of IFNs worked together to develop practical guidelines for the use of IFNs. Practical recommendations were developed for patient education on the use of IFN; initial patient assessment and monitoring, including contraindications to the use of IFN, monitoring and managing adverse events, and IFN dose modification and discontinuation; IFN injection procedures; treatment of elderly patients; and use during pregnancy and nursing. Successful adjuvant therapy of melanoma with high-dose IFN requires close compliance with the treatment regimen. Recommendations for the recognition and management of adverse events are designed to enable more patients to complete the full planned course of treatment.

Dréno B, Wallon-Dumont G. · Unité de cancéro-dermatologie, Clinique dermatologique, CHU Hôtel-Dieu, Nantes. · Presse Med. · Pubmed #12610396 No free full text.

Abstract: At the stage of primary tumour and lymph node extension, the treatment of melanoma is mainly surgical. Interferon alpha has obtained marketing authorisation to be used as adjuvant therapy at different doses in the treatment of these two stages of the disease and must therefore be discussed with the patient. At the metastatic stage, no real progress in chemotherapy has been noted for more than 20 years. Combined therapy with chemotherapy and cytokines (interferon alpha or interleukine 2) increases the percentage of response but without increasing the overall survival. THREE IMMUNOTHERAPY TECHNIQUES: Cellular immunotherapy represents the main hope of these future years in the treatment of melanoma, with the injection of in vitro expanded cytotoxic T cells, vaccination and dendritic cells. Although clinical results are starting to be published, cellular immunotherapy remains in the field of clinical research, within the framework of clinical trials.

Dréno B. · Clinique dermatologique CHRU L'hôtel-Dieu, Nantes. · Rev Prat. · Pubmed #10337195 No free full text.

Abstract: Melanoma has the worst pronostic among the cutaneous tumours. Many patients die with this tumour. It is the cancer whose incidence increases the most among all the tumours (double every 10 years). The pronostic of melanoma is very bad at metastatic stage. On the contrary, the excision of tumour at an early stage may be associated to a complete remission. So it is important to encourage skin cancer detection for an early treatment of melanoma. Finally, it appears crucial to increase the diffusion of informations about the photoprotection. Indeed, solar exposition probably plays on important role in the increasing incidence fo this skin tumour.

van Baren N, Bonnet MC, Dréno B, Khammari A, Dorval T, Piperno-Neumann S, Liénard D, Speiser D, Marchand M, Brichard VG, Escudier B, Négrier S, Dietrich PY, Maraninchi D, Osanto S, Meyer RG, Ritter G, Moingeon P, Tartaglia J, van der Bruggen P, Coulie PG, Boon T. · Ludwig Institute for Cancer Research, 74 avenue Hippocrate, UCL7459, B-1200 Brussels, Belgium; e-mail: · J Clin Oncol. · Pubmed #16061912 No free full text.

Abstract: PURPOSE: To evaluate the toxicity, antitumoral effectiveness, and immunogenicity of repeated vaccinations with ALVAC miniMAGE-1/3, a recombinant canarypox virus containing a minigene encoding antigenic peptides MAGE-3(168-176) and MAGE-1(161-169), which are presented by HLA-A1 and B35 on tumor cells and can be recognized by cytolytic T lymphocytes (CTLs). MATERIALS AND METHODS: The vaccination schedule comprised four sequential injections of the recombinant virus, followed by three booster vaccinations with the MAGE-3(168-176) and MAGE-1(161-169) peptides. The vaccines were administered, both intradermally and subcutaneously, at 3-week intervals. RESULTS: Forty patients with advanced cancer were treated, including 37 melanoma patients. The vaccines were generally well tolerated with moderate adverse events, consisting mainly of transient inflammatory reactions at the virus injection sites. Among the 30 melanoma patients assessable for tumor response, a partial response was observed in one patient, and disease stabilization in two others. The remaining patients had progressive disease. Among the patients with stable or progressive disease, five showed evidence of tumor regression. A CTL response against the MAGE-3 vaccine antigen was detected in three of four patients with tumor regression, and in only one of 11 patients without regression. CONCLUSION: Repeated vaccination with ALVAC miniMAGE-1/3 is associated with tumor regression and with a detectable CTL response in a minority of melanoma patients. There is a significant correlation between tumor regression and CTL response. The contribution of vaccine-induced CTL in the tumor regression process is discussed in view of the immunologic events that could be analyzed in detail in one patient.

Kruit WH, van Ojik HH, Brichard VG, Escudier B, Dorval T, Dréno B, Patel P, van Baren N, Avril MF, Piperno S, Khammari A, Stas M, Ritter G, Lethé B, Godelaine D, Brasseur F, Zhang Y, van der Bruggen P, Boon T, Eggermont AM, Marchand M. · Erasmus Medical Center-Daniel den Hoed Cancer Center, Department of Internal Oncology, Rotterdam, The Netherlands. · Int J Cancer. · Pubmed #15945101 No free full text.

Abstract: The purpose of this phase 1/2 study was to evaluate toxicity, tumor evolution and immunologic response following administration of a fixed dose of a recombinant MAGE-3 protein by subcutaneous and intradermal routes in the absence of immunologic adjuvant. Thirty-two patients with detectable metastatic melanoma expressing gene MAGE-3 were included and 30 received at least one injection with a fixed dose of a ProtD-MAGE-3 fusion protein. The immunization schedule included 6 intradermal and subcutaneous injections at 3-week intervals. Afterward, patients without major tumor progression who required other treatments received additional vaccinations at increasing time intervals. The vaccine was generally well tolerated. Among the 26 patients who received at least 4 vaccinations, we observed 1 partial response and 4 mixed responses. For these 5 responding patients, time to progression varied from 3.5 to 51+ months. An anti-MAGE-3 CD4 T-lymphocyte response was detected in 1 out of the 5 responding patients. The majority of patients had no anti-MAGE-3 antibody response. The clinical and immunologic responses generated by the vaccine are rather limited. Nevertheless, given the potential antitumor efficacy and the very mild toxicity of vaccinations, further studies combining MAGE proteins and/or peptides with potent immunologic adjuvants are warranted, not only in metastatic melanoma, but also in the adjuvant setting.

Dréno B, Nguyen JM, Khammari A, Pandolfino MC, Tessier MH, Bercegeay S, Cassidanius A, Lemarre P, Billaudel S, Labarrière N, Jotereau F. · Skin Cancer Unit, CHR Hôtel Dieu, Nantes, 44093 Nantes, France. · Cancer Immunol Immunother. · Pubmed #12384805 No free full text.

Abstract: The aim of this study was to demonstrate the interest of using tumor-infiltrating lymphocytes (TIL) as adjuvant therapy for stage III (regional lymph nodes) melanoma. After lymph node excision, patients without any detectable metastases were randomly assigned to receive either TIL plus interleukin-2 (IL-2) for 2 months, or IL-2 only. The primary endpoint was determination of the duration of the relapse-free interval. Eighty-eight patients determined as eligible for treatment were enrolled in the study. After a median follow-up of 46.9 months, for the study population the analysis did not show a significant extension of the relapse-free interval or overall survival. However, a significant interaction ( P<0.001) was found between the treatment and the number of invaded lymph nodes. In the group with only one invaded lymph node, the estimated relapse rate was significantly lower ( P(adjusted)=0.0285) and the overall survival was increased ( P(adjusted)=0.039) in the TIL+IL-2 arm compared with the IL-2 only arm. No differences between the two arms, either as regards the duration of disease-free survival or overall survival, were noted in the group with more than one invaded lymph node whatever the number of invaded lymph nodes. Treatment was compatible with normal daily activity. This study demonstrates for the first time that the efficiency of TIL in stage III melanoma (AJCC) is directly related to the number of invaded lymph nodes, indicating that tumor burden might be a crucial factor in the efficacy and/or in vitro expansion of T cells specific for autologous tumor antigen, a finding which could be of value in future vaccine development for the treatment of melanoma.

Labarrière N, Pandolfino MC, Gervois N, Khammari A, Tessier MH, Dréno B, Jotereau F. · Unité INSERM U463, 9 Quai Moncousu, 44093 Nantes Cedex 1, France. · Cancer Immunol Immunother. · Pubmed #12384804 No free full text.

Abstract: Adoptive therapy for cancer using tumor-infiltrating lymphocytes (TIL) has mainly been investigated in cancer patients with advanced stage disease. The limited clinical success has not been encouraging, although this might be explained by poor TIL specificity and/or high tumor burden. To re-evaluate the effectiveness of adoptive therapy, we analyzed the capacity of tumor-reactive TIL injection in preventing the further development of disease in stage III melanoma patients after complete tumor resection. A phase II/III randomized trial was performed on 88 melanoma patients, who received autologous TIL plus interleukin-2 (IL-2) or IL-2 only. The duration of relapse-free survival was analyzed, taking into account the immunological specificity of injected TIL and the number of metastatic lymph nodes removed before treatment. Kaplan-Meyer analysis revealed that the injection of tumor-reactive TIL was statistically correlated with prolonged relapse-free survival in patients with only one metastatic lymph node. Therefore, improved clinical outcome could be obtained after adoptive therapy by selecting appropriate groups of patients and monitoring the specificity of the injected TIL populations.

Marchand M, van Baren N, Weynants P, Brichard V, Dréno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Liénard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jäger E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T. · Ludwig Institute for Cancer Research, Brussels Branch, and Université Catholique de Louvain, Belgium. · Int J Cancer. · Pubmed #9935203 No free full text.

Abstract: Thirty-nine tumor-bearing patients with metastatic melanoma were treated with 3 subcutaneous injections of the MAGE-3.A1 peptide at monthly intervals. No significant toxicity was observed. Of the 25 patients who received the complete treatment, 7 displayed significant tumor regressions. All but one of these regressions involved cutaneous metastases. Three regressions were complete and 2 of these led to a disease-free state, which persisted for more than 2 years after the beginning of treatment. No evidence for a cytolytic T lymphocyte (CTL) response was found in the blood of the 4 patients who were analyzed, including 2 who displayed complete tumor regression. Our results suggest that injection of the MAGE-3.A1 peptide induced tumor regression in a significant number of the patients, even though no massive CTL response was produced.

Lacreusette A, Barbieux I, Nguyen JM, Pandolfino MC, Dréno B, Jacques Y, Godard A, Blanchard F. · INSERM U892, Centre de Recherche en Cancérologie, Nantes F-44035, France. · J Pathol. · Pubmed #19097071 No free full text.

Abstract: Stage III melanoma is refractory to common therapies and shows resistance to the anti-proliferative activity of cytokines in vitro. We previously demonstrated that, for 30% of the metastatic melanoma cell lines, oncostatin M (OSM) resistance is due to the epigenetic silencing of its receptor OSMRbeta. Here we analyse, on a larger panel of short-term cultures derived from melanoma-invaded lymph nodes, other mechanisms potentially implicated in OSM resistance. For 18% of the cell lines, OSM resistance is associated with a phosphorylation defect of signal transducer and activator of transcription (STAT)3 on serine (Ser)727, in concordance with defects in the activation of various protein kinase C (PKC) isoforms, especially PKCdelta. For 21% of the cell lines, OSM resistance is associated with a defect in the activation of Akt on Ser473. By the use of inhibitors, dominant negatives and small interfering (si)RNA, we show that the PKC-STAT3 Ser727, but not the Akt, pathway appears necessary for OSM anti-proliferative activity. Moreover, we bring evidence that OSM or interleukin (IL)-6, produced in lymph nodes and/or melanoma cells, could be involved in the establishment of OSM resistance during melanoma progression. These findings could be relevant for the prognosis and the treatment of stage III melanoma patients.

Lacreusette A, Lartigue A, Nguyen JM, Barbieux I, Pandolfino MC, Paris F, Khammari A, Dréno B, Jacques Y, Blanchard F, Godard A. · INSERM U892, Centre de Recherche en Cancérologie, Nantes F-44035, France. · J Pathol. · Pubmed #18798220 No free full text.

Abstract: 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) gamma or tumour necrosis factor (TNF) alpha 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.

Bouquié R, Bonnin A, Bernardeau K, Khammari A, Dréno B, Jotereau F, Labarrière N, Lang F. · INSERM U892, 9 quai Moncousu, 44093, Nantes Cedex 1, France. · Cancer Immunol Immunother. · Pubmed #18751701 No free full text.

Abstract: HLA multimers are now widely used to stain and sort CD8 T lymphocytes specific for epitopes from viral or tumoral antigens presented in an HLA class I context. However, the transfer of this technology to a clinical setting to obtain clinical grade CD8 T lymphocytes that may be used in adoptive cell transfer (ACT) is hindered by two main obstacles: the first obstacle is the use of streptavidin or derived products that are not available in clinical grade to multimerize HLA/peptide monomers and the second is the reported high degree of apoptosis that eventually occurs when T cell receptors are crosslinked by HLA multimers. In the present report, we describe new HLA multimers composed of immunomagnetic beads covalently coupled to a mAb specific for the AviTag peptide and coated with HLA/peptide monomers bearing the non biotinylated AviTag at the COOH terminus of the HLA heavy chain. Thus, all the components of this new reagent can be obtained in clinical grade. We compared these new multimers with the previously described multimers made with streptavidin beads coated with biotinylated HLA/peptide monomers, in terms of sorting efficiency, recovery of functional T cells, apoptosis and activation. We provide evidence that the new multimers could very efficiently sort pure populations of T lymphocytes specific for three different melanoma antigens (Melan-A, gp100 and NA17-A) after a single peptide stimulation of melanoma patients' PBMC. The recovered specific T cells were cytotoxic against the relevant melanoma cell-lines and, in most cases, produced cytokines. In addition, in marked contrast with streptavidin-based multimers, our new multimers induced very little apoptosis or activation after binding specific T lymphocytes. Altogether, these new multimers fulfill all the necessary requirements to select clinical grade T lymphocytes and should facilitate the development of ACT protocols in cancer patients.

Knol AC, Lemaître F, Pandolfino MC, Volteau C, Quéreux G, Saiagh S, Khammari A, Viguier M, Dréno B. · INSERM, U601, 9 Quai Moncousu Nantes Cedex 01, France. · Exp Dermatol. · Pubmed #18312383 No free full text.

Abstract: The exact role of CD4+CD25(high) regulatory T cells (Treg) in adoptive immunotherapy of melanoma is still to be determined, and an association between an expansion of Treg cells and the expansion of therapeutic tumor-infiltrating lymphocytes (TIL) remains unelucidated. In this context, the aim of our study was to determine whether functional Treg cells were detectable and amplified among in vitro-expanded TIL from 10 metastatic melanoma lymph nodes (LNs). In this study, we investigated the expression of forkhead/winged helix transcription factor 3 (Foxp3) in melanoma-invaded LNs and determined proportion and functionality of Treg cells among TIL extracted from these 10 metastatic melanoma LNs at different steps of their in vitro expansion. We found that metastatic melanoma LNs expressed very heterogeneous levels of Foxp3 and that CD4+CD25(high) Treg cells extracted from these LNs were detectable at each step of the in vitro culture of TIL but decreasing during the culture. In addition, functional assays demonstrated that these CD4+CD25(high) T cells were capable of suppressing autologous CD8+ and CD4+CD25- T cell proliferation. These cells were indeed Treg cells as they expressed Foxp3. In conclusion, our work suggests that CD4+CD25(high) Foxp3 expressing T cells are not expanded during in vitro amplification of TIL obtained from melanoma-invaded LNs.

Quéreux G, Brocard A, Dréno B. · Service de Dermatologie, Hôtel-Dieu, 1, place Alexis Ricordeau, 44093 Nantes Cedex 1. · Ann Dermatol Venereol. · Pubmed #18166926 No free full text.

This publication has no abstract.

Khammari A, Nguyen JM, Pandolfino MC, Quereux G, Brocard A, Bercegeay S, Cassidanius A, Lemarre P, Volteau C, Labarrière N, Jotereau F, Dréno B. · Skin Cancer Unit, CHU Hôtel Dieu, Nantes, Place Alexis Ricordeau, 44093, Nantes Cedex 01, France. · Cancer Immunol Immunother. · Pubmed #17549472 No free full text.

Abstract: The first analysis of our clinical trial on interest of using tumor-infiltrating lymphocytes (TIL) as adjuvant therapy for stage III (regional lymph nodes) melanoma was published in 2002 [5]. The aim of this paper is to update clinical results of 7 years of follow-up after the last treated patient. In the trial conducted between December 1993 and January 1999, patients without any detectable metastases after lymph node excision were randomly assigned to receive either TIL plus interleukin-2 (IL-2) for 2 months, or IL-2 only. The duration of the relapse-free interval was the primary objective. Eighty-eight patients were enrolled in the study. Currently, the last analysis performed in June 2006, after a median follow-up of 114.8 months, did not show change of non-significant extension of the relapse-free interval or overall survival. However, this second analysis strengthens our first hypothesis about the relationship between number of invaded lymph nodes and TIL treatment effectiveness. In the group with only one invaded lymph node, the estimated relapse rate was significantly lower (P (adjusted) = 0.0219) and the overall survival was increased (P (adjusted) = 0.0125) in the TIL+IL-2 arm compared with the IL-2 only arm. No differences between the two arms, either with regard to the duration of disease-free survival (P (adjusted) = 0.38) or overall survival (P (adjusted) = 0.43), were noted in the group with more than one invaded lymph node, whatever the number of invaded lymph nodes. Treatment was compatible with normal daily activity. This study, with a very long follow up (median of almost 10 years), postulates for the first time relationship between TIL efficiency in stage III melanoma (AJCC) and number of invaded lymph nodes, indicating that tumor burden might be a crucial factor in the production of an effective in vitro expansion of T cells specific for autologous tumor antigen, a finding which could be of value in future vaccine development for the treatment of melanoma.

Toulemonde A, Quereux G, Dréno B. · Service de Dermatologie, CHU d'Angers. · Ann Dermatol Venereol. · Pubmed #15041843 No free full text.

Abstract: BACKGROUND: The side effects attributed to interferon alpha are numerous, including autoimmune events such as lupus, arthritis or thyroiditis. Emergence of sarcoidosis in patients with interferon alpha therapy is much more rare. We describe a case occurring in a patient treated for melanoma. CASE REPORT: A 54 Year-old woman who had been treated for fifty Months with low dose interferon alpha (Roféron(R), 3 millions units, three times a week) for a melanoma of the scalp (adjuvant therapy), developed labial nodules on a permanent tattoo. The diagnosis of sarcoid granuloma was confirmed by histopathologic analysis. Physical examination revealed dyspnea on exertion with a moderate pulmonary interstitial infiltrate on the CT Scan. The diagnosis of cutaneous and pulmonary sarcoidosis in association with interferon alpha therapy was made. Within 4 weeks, skin nodules began to regress although interferon was pursued at the same dose. Four Months later, at the end of interferon therapy, the nodules had totally disappeared. DISCUSSION: About forty cases of cutaneous or systemic sarcoidosis in patients treated with interferon alpha have been reported, but none of these cases concerned patients treated for melanoma. Interferon alpha might promote the development of sarcoid granuloma by inducing a switch of cytokine secretion from a Th2 to a Th1 cytokine pattern. It is very important to recognize cutaneous sarcoidosis during interferon alpha treatment because pulmonary sarcoidosis can be confused with common general side effects observed with such treatment.

Karanikas V, Lurquin C, Colau D, van Baren N, De Smet C, Lethé B, Connerotte T, Corbière V, Demoitié MA, Liénard D, Dréno B, Velu T, Boon T, Coulie PG. · Cellular Genetics Unit, Institute of Cellular Pathology, Université de Louvain, Brussels, Belgium. · J Immunol. · Pubmed #14568971 links to  free full text

Abstract: We have analyzed the T cell responses of HLA-A1 metastatic melanoma patients with detectable disease, following vaccination with a recombinant ALVAC virus, which bears short MAGE-1 and MAGE-3 sequences coding for antigenic peptides presented by HLA-A1. To evaluate the anti-MAGE CTL responses, we resorted to antigenic stimulation of blood lymphocytes under limiting dilution conditions, followed by tetramer analysis and cloning of the tetramer-positive cells. The clones were tested for their specific lytic ability and their TCR sequences were obtained. Four patients who showed tumor regression were analyzed, and an anti-MAGE-3.A1 CTL response was observed in three of these patients. Postvaccination frequencies of anti-MAGE-3.A1 CTL were 3 x 10(-6), 3 x 10(-3), and 3 x 10(-7) of the blood CD8 T cells, respectively. These three responses were monoclonal. No anti-MAGE-1.A1 CTL response was observed. These results indicate that, like peptide immunization, ALVAC immunization produces monoclonal responses. They also suggest that low-level antivaccine CTL responses can initiate a tumor regression process. Taken together, our analysis of anti-MAGE-3.A1 T cell responses following peptide or ALVAC vaccination shows a degree of correlation between CTL response and tumor regression, but firm conclusions will require larger numbers.

Wallon-Dumon G, Dréno B. · Clinique dermatologique, CHU Hôtel-dieu, Nantes. · Presse Med. · Pubmed #12610395 No free full text.

Abstract: EARLY DIAGNOSIS FOR EFFICIENT MANAGEMENT: The melanoma is a cutaneous tumour of poor prognosis and its incidence is increasing. Some risk factors are now well established ( field, phototype, family history) and its early discovery is clinically possible since the lesions are visible to the eye. When diagnosed early, the prognosis is clearly improved. CLINICAL FORMS OF VARYING PROGNOSIS: Depending on the clinical, histopathological and progressive differences, it is possible to distinguish a Superficial Spreading Melanoma (60 to 70%), nodular melanoma (10 to 15%), Dubreuilh's melanoma (5 to 10%) and acrolentigenous melanoma (5%). Apart from these 4 major clinical forms, there is also the sub-ungual melanoma and the mucosal melanoma. Particular situations may also exist: the discovery of metastasis without identification of cutaneous tumour, a melanoma in a pregnant woman or a child, a familial melanoma or multiple melanomas. THE ELEMENTS OF DIAGNOSIS: The semiological analysis of an often-pigmented lesion of the skin, relying on the ABCDE rule and the notion of rapid progression, is the first stage in the diagnostic approach. It is completed, following complete exeresis, by anatomopathological exploration (Breslow's index, existence of ulceration, signs of regression, Clark's classification, histological type and mitotic activity). Two further elements should also be taken into account: the results of a dermatoscopy and the analysis of the sentinel nodes.

Dréno B, Wallon-Dumont G. · Unité de cancéro-dermatologie, Clinique dermatologique, CHU Hôtel-Dieu, Nantes. · Presse Med. · Pubmed #12610394 No free full text.

Abstract: A WORRYING INCIDENCE: In frequency, the melanoma, is placed just after breast, colic and pulmonary cancer with around 6 000 new cases per year in France. Moreover, it is the tumour that is increasing the most and its frequency has doubled over the past 10 years. It is presently estimated as 7 to 9/100 000 in France. THE IMPACT OF PREVENTIVE MEASURES: Primary and secondary prevention is therefore crucial, as is the identification of patients at risk. However, till now, the impact of educational and preventive campaigns with regard to sun exposure, which plays a major role in the development of a melanoma, are still insufficient

Pandolfino MC, Labarrière N, Tessier MH, Cassidanius A, Bercegeay S, Lemarre P, Dehaut F, Dréno B, Jotereau F. · Unité de Thérapie Cellulaire et Génique, CHRU de Nantes, 9 Quai Moncousu, 44093 Nantes, France. · Cancer Immunol Immunother. · Pubmed #11419180 No free full text.

Abstract: The rationale of treating melanoma patients by infusion with tumor-infiltrating leukocytes (TIL) is to perform an adoptive therapy through injection of tumor-specific T cells. Nonetheless, methods currently used for ex vivo TIL expansion have not been evaluated for their efficacy to expand TAA-specific T cells. We have addressed this question here, using a culture method in which high TIL growth was induced by a polyclonal T cell stimulus. Intracellular cytokine assays were performed to measure the proportion of T cells responding to autologous tumor cells among the lymphocytes from lymph node biopsies (TIL) of 26 patients with stage III melanoma. The data show that TIL from 18 of these patients contained detectable amounts of tumor-specific T cells before expansion. Although they decreased somewhat in percent abundance during expansion, they were still present afterwards, ranging from 0.3 to 13.8%. Since a median number of 1.7 x 10(10) TIL was obtained from these patients (starting from 3.6 x 10(6) TIL), a total amount of tumor-reactive cytokine-secreting TIL of between 2.8 x 10(6) and 1.12 x 10(9) was obtained in each case from 18 patients. The TIL populations from 8 patients did not contain tumor-reactive T cells: neither before expansion, nor after expansion. Lack of tumor-reactive TIL only occurs for patients bearing several tumor-invaded lymph nodes (40%), but not for those having a single invaded lymph node. Therefore, high numbers of tumor-reactive T cells can be produced, through a polyclonal TIL stimulation, from most early stage III melanoma patients but from only about half of the patients with a more disseminated disease. For this last group, the possibility of getting tumor-reactive TIL can be predicted by checking the presence of these cells before expansion.

Denis MG, Masson D, Tessier MH, Dréno B, Lustenberger P. · No affiliation provided · Melanoma Res. · Pubmed #12140387 No free full text.

This publication has no abstract.