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In the last few years, the importance of neoantigens in the development of personalized antitumor vaccines has increased remarkably. In order to study whether bioinformatic tools are effective in detecting neoantigens that generate an immune response, DNA samples from patients with cutaneous melanoma in different stages were obtained, resulting in a total of 6048 potential neoantigens gathered. Thereafter, the immunological responses generated by some of those neoantigens ex vivo were tested, using a vaccine designed by a new optimization approach and encapsulated in nanoparticles. Our bioinformatic analysis indicated that no differences were found between the number of neoantigens and that of non-mutated sequences detected as potential binders by IEDB tools. However, those tools were able to highlight neoantigens over non-mutated peptides in HLA-II recognition (p-value 0.03). However, neither HLA-I binding affinity (p-value 0.08) nor Class I immunogenicity values (p-value 0.96) indicated significant differences for the latter parameters. Subsequently, the new vaccine, using aggregative functions and combinatorial optimization, was designed. The six best neoantigens were selected and formulated into two nanoparticles, with which the immune response ex vivo was evaluated, demonstrating a specific activation of the immune response. This study reinforces the use of bioinformatic tools in vaccine development, as their usefulness is proven both in silico and ex vivo.

espanolIntroduccion: El carcinoma de celulas de Merkel (CCM) es una neoplasia cutanea infrecuente y de pronostico pobre. No hay consenso para abordar su manejo. Material y metodos: Realiza-mos una busqueda de pacientes con diagnostico histologico de CCM entre 1998 y 2018 (n = 20), en la base de datos de nuestro hospital. Recogimos las siguientes variables: sexo, edad, historia de inmunosupresion y de cancer cutaneo no melanoma y me-lanoma maligno, sospecha diagnostica inicial, tamano tumoral, localizacion, estadificacion, tratamientos recibidos, evolucion y supervivencia. Resultados: La mayoria de las lesiones (40%) se localizaban en la cabeza y cuello, y 50% tenian un tamano de 2 a 5 cm. Ochenta y cinco por ciento de los pacientes recibio tratamiento quirurgico y 75% radioterapia. Cincuenta por ciento de los pacientes presentaron recidivas, todas en los primeros dos anos. Hemos observado que la supervivencia es mayor en los pacientes con lesiones menores de 2 cm, localizadas en extremidades, con positividad para poliomavirus, en los que recibieron radioterapia adyuvante y no presentan margenes quirurgicos afectados. Conclusiones: Hemos identificado cinco factores asociados con una mayor supervivencia que, aunque no son estadisticamente significativos (por el tamano muestral), son clinicamente relevantes y coinciden con los de otras series. EnglishIntroduction: Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with a poor prognosis. There is no consensus to address its management. Material and methods: We performed a search of patients with histological diagnosis of MCC from 1998 to 2018 (n = 20), in the database of our hospital and we collected next data: sex, age, history of immunosuppression, skin cancer no melanoma and malignant melanoma, initial diagnosis suspicion, tumor size, location, staging, treatments received, evolution and survival. Results:The majority of lesions (40%) were located in the face and neck and 50% had 2 to 5 cm. 85% of the patients received surgical treatment, 75% had RT. 50% of patients had recurrence, all before the first 24 months. In our sample, we observed that survival is greater in patients with lesions smaller than 2 cm, located in extremities, positive for polyomavirus, in those who have received adjuvant RT and in those without affected surgical. Conclusions: We have observed five factors associated with grater survival, which, although not statistically significant, are clinically relevant and concur with those of other series

espanolIntroduccion: La hidradenitis supurativa (HS) es una dermatosis inflamatoria cronica que afecta a la unidad pilosebacea en las grandes areas intertriginosas. La inflamacion cronica de larga evolucion favorece el desarrollo del carcinoma de celulas escamosas (CCE) sobre lesiones de HS. Esta complicacion es mas frecuente en varones y en las regiones glutea o perineal. Caso clinico: Varon de 57 anos con HS grave (Hurley III) con >30 anos de evolucion, de predominio en gluteos y resistente a multiples tratamientos; desarrollo un carcinoma epidermoide infiltrante sobre lesiones de HS. Al momento del diagnostico mostraba adenopatias locorregionales de gran tamano. Se descarto el tratamiento quirurgico o radioterapico y se trato con quimioterapia paliativa. Discusion: La infeccion por el virus del papiloma humano (HPV) y otros cofactores parecen intervenir en la transformacion maligna de las lesiones. El retraso diagnostico y una alta capacidad de proyectar metastasis le confieren al carcinoma epidermoide sobre la HS un mal pronostico y elevada mortalidad. Conclusion: Ante una HS avanzada, de larga evolucion y resistente al tratamiento, sobre todo si asienta en la region glutea, se deben tomar multiples biopsias profundas para detectar de manera temprana el desarrollo de un posible carcinoma epidermoide sobre las lesiones. EnglishIntroduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects the folliculosebaceous unit in large intertriginous body areas. Longstanding inflammation might lead to the development of a squamous cell carcinoma arising in HS lesions, which is more likely to occur in males and at the gluteal or perineal sites. Case report: A 57-year-old man with an over 30-year history of severe HS (Hurley III) involving the buttocks and refractory to a wide variety of treatments developed a squamous cell carcinoma over HS lesions. He presented large locoregional lymphadenopathies at diagnosis. Surgery and radiotherapy were dismissed and he was treated with palliative chemotherapy. Discussion: Human papillomavirus (HPV) and other cofactors seem to be involved in the malignant transformation of the lesions. Due to the common delayed diagnosis and its high metastatic ability, prognosis is poor and mortality rates high. Conclusion: Areas of non-healing wounds should be cautiously observed and multiple deep biopsies carried out in patients suffering from longstanding and resistant HS, especially if they involve the buttocks or perineum, in order to detect the development of a squamous cell carcinoma arising in HS lesions at an early stage.

Importance Hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and environmental factors. Objectives To analyze the association between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE and the severity of hypertriglyceridemia during bexarotene therapy and to optimize patient selection for bexarotene therapy based on adverse effect profile. Design, Setting, and Participants This case series study was conducted in 12 university referral hospitals in Spain from September 17, 2014, to February 6, 2015. One hundred twenty-five patients with a confirmed diagnosis of CTCL who had received bexarotene therapy for at least 3 months were enrolled. Nine patients were excluded owing to missing analytic triglyceride level data, leaving a study group of 116 patients. Data on demographic and cardiovascular risk factor were collected, and a complete blood analysis, including lipid profile and genetic analysis from a saliva sample, was performed. Main Outcomes and Measures Primary outcomes were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied. Results Among 116 patients, the mean (SD) age was 61.2 (14.7) years, 69 (59.5%) were men, and 85 (73.2%) had mycosis fungoides, the most prevalent form of CTCL. During bexarotene therapy, 96 patients (82.7%) experienced hypertriglyceridemia, which was severe or extreme in 8 of these patients (8.3%). Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations. After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). Conclusions and Relevance These results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.

The choice of treatment in cutaneous T-cell lymphomas (CTCLs) depends on the clinical stage of the disease and the patient's general condition. To date, there is no curative treatment for this disease, and the objective is to control the symptoms and prevent the disease from progressing. Bexarotene is an X receptor-specific retinoid with anti-tumor activity. Its use as treatment for CTCLs refractory to at least one prior systemic therapy has been approved by the FDA.We carried out a descriptive study of 9 patients treated with bexarotene in the Lymphoma Unit of our department. We analyzed the clinical characteristics of the patients and the efficacy of the treatment, and we collected data on the side effects that appeared.The overall response to the treatment was 44.4% (4/9). 2 patients had full remission and 2 had partial remission. Tolerance to the treatment was good, and the most frequent side effects were hypertriglyceridemia, hypercholesterolemia and central hypothyroidism.Even though this is a series of only 9 patients, the results that we obtained are similar to ones previously described. Bexarotene is an effective therapeutic option in this heterogeneous group of diseases.