Maladie de Verneuil et zinc (une nouvelle approche thérapeutique)

La maladie de Verneuil est une dermatose rare et mal connue. Elle réalise au niveau des régions axillaires, inguinales, périnéo-fessière et mammaires des abcès profonds avec écoulements itératifs. L' évolution est chronique, se faisant par poussées, et laissant des fistules et brides cicatricielles. Cela constitue une gêne considérable dans la vie du patient. La physiopathogénie de la maladie de Verneuil est encore sujette à controverse. Actuellement, la plupart des auteurs évoquent l' occlusion du follicule pileux comme premier événement pathogène de cette maladie. Le traitement médical de la maladie de Verneuil n' est pas consensuel, entraînant le plus souvent une efficacité modérée ou transitoire. Nous rapportons une étude rétrospective de 22 patients traités par forte dose de gluconate de zinc avec une très bonne efficacité et tolérance.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Tissue biomarkers in melanoma patients treated with TIL.

While treating stage III melanoma patients with autologous therapeutic TIL in an adjuvant setting, we previously reported a significant benefit of treatment on both progression-free survival and overall survival in patients with only one invaded lymph node (early stage III) compared to patients with more than one invaded lymph nodes (advanced stage III). In this context, in order to understand the difference of activity of TIL therapy according to the progression of the illness at stage III, the first objective of the present study was to determine potential differences in the characteristics of TIL populations obtained from an early stage III and a more advanced stage III when tumor burden is more important. The second objective was to determine possible differences in tissue expression level of several molecules involved in interactions between tumor cells and T cells between early and advanced stage III considering that the tumor microenvironment of invaded lymph nodes could become more tolerant with the progression of the disease. A total of 47 samples of melanoma invaded LN from stage IIIb (AJCC 2007) melanoma patients treated with TIL plus IL-2 were included in this study. We confirmed that both PFS and OS were significantly associated to the presence of tumor-reactive T-cells among TIL injected to the patients and that these tumor reactive T cells were more frequently observed at the early stage III. Moreover, while analyzing the expression of 17 markers on 34/47 tumor specimens using immunohistochemistry, we identified that 3 tissue markers involved in interactions between melanoma cells and T cells have a significant difference of expression between early and advanced stage III: MHC class I, adhesion molecule ICAM-1 and the co-stimulation molecule LFA-3 had a significantly weaker expression in melanoma tissue specimens from advanced stage III. In addition, the expression of the alpha chain of the IL-2 receptor (CD25) and the nuclear transcription factor Foxp3 was significantly increased in the melanoma tissue specimens from advanced stage III. Our results suggest differences in the immunological status of the tumor microenvironment between early and advanced stage III, which could explain the difference in clinical response to TIL infusion in an adjuvant setting between early and advanced stage III

Treatment of Metastatic Melanoma with Autologous Melan-A/Mart-1-Specific Cytotoxic T Lymphocyte Clones

International audienceImmunotherapy by adoptive T-cell transfer aims at maximizing tumor antigen-specific T-cell responses. We treated 14 patients at the metastatic stage in a phase II study with Melan-A-specific T-cell clones generated from patient blood. During the period required for T-cell clone generation, the patients were treated by dacarbazine. Every patient received a T-cell clone suspension followed by subcutaneous injections of interleukin 2 and interferon alpha. Patients were monitored until disease progression occurred. We succeeded in obtaining autologous Melan-A-specific cytotoxic T lymphocyte clones, which were highly reactive against tumor cells for all the patients. Of the 14 patients treated, six (43%) experienced an objective response (CR þ PR) with long-term complete remission for two patients (1 CR for 5 years and 1 CR for 28 months). Furthermore, we showed that all the clinical responses were significantly associated with in vivo expansion of the Melan-A-specific T-cell repertoire. This phenomenon appeared to be significantly associated with clinical responses. Thus, over the course of an adoptive cell transfer, monitoring this melanoma-specific T-cell expansion in patient blood appears crucial for predicting the clinical efficiency of such an immunological approach

Long-term follow-up of patients treated by adoptive transfer of melanoma tumor-inWltrating lymphocytes as adjuvant therapy for stage III melanoma

International audienceThe 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-signiWcant 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 eVectiveness. In the group with only one invaded lymph node, the estimated relapse rate was signiWcantly 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 diVerences 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 Wrst time relationship between TIL eYciency 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 eVective in vitro expansion of T cells speciWc for autologous tumor antigen, a finding which could be of value in future vaccine development for the treatment of melanoma

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n=4) or IV (n=6) melanoma. All but 1 patient with unresectable stage III melanoma (1st line) had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation

Severe dermatophytosis in solid organ transplant recipients: A French retrospective series and literature review

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