Browsing by Subject "Immunotherapy"

Now showing 1 - 8 of 8
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    Advances of MUC1 as a target for breast cancer immunotherapy
    (Murcia : F. Hernández, 2007) Yang, E.; Hu, X.F.; Xing, P.X.
    MUC1 is a potential target in breast cancer immunotherapy as MUC1 is overexpressed in breast cancer, and is absent or expressed in low level in normal mammary gland. In addition, MUC1 is mostly aberrantly underglycosylated in cancer and the antigens on the cancer surface are different from normal cell. Therefore targeting MUC1 for cancer immunotherapy can exploit the difference between cancer and normal cells, and eliminating the cancerous cells while leaving the normal mammary cells unharmed. This review will focus on the recent advance of MUC1 breast cancer immunotherapy currently being investigated.
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    Circulating blood biomarkers correlated with the prognosis of advanced triple negative breast cancer
    (BioMed Central, 2024-01-13) Li, Xingyu; Zhang, Yanyan; Zhu, Cheng; Xu, Wentao; Hu, Xiaolei; Sánchez Martínez, Domingo Antonio; Alonso Romero, José Luis; Yan, Ming; Dai, Ying; Wang, Hua; Medicina
    Background Immune checkpoint inhibitors (ICIs) can improve survivals of metastatic triple negative breast cancer (mTNBC); however, we still seek circulating blood biomarkers to predict the efficacy of ICIs. Materials and methods In this study, we analyzed the data of ICIs treated mTNBC collected in Anhui Medical University affiliated hospitals from 2018 to 2023. The counts of lymphocytes, monocytes, platelets, and ratio indexes (NLR, MLR, PLR) in peripheral blood were investigated via the Kaplan-Meier curves and the Cox proportional-hazards model. Results The total of 50 mTNBC patients were treated with ICIs. High level of peripheral lymphocytes and low level of NLR and MLR at baseline and post the first cycle of ICIs play the predictable role of immunotherapies. Lymphocytes counts (HR = 0.280; 95% CI: 0.095–0.823; p = 0.021) and NLR (HR = 1.150; 95% CI: 1.052–1.257; p = 0.002) are significantly correlated with overall survival. High NLR also increases the risk of disease progression (HR = 2.189; 95% CI:1.085–4.414; p = 0.029). When NLR at baseline ≥ 2.75, the hazard of death (HR = 2.575; 95% CI:1.217–5.447; p = 0.013) and disease progression (HR = 2.189; 95% CI: 1.085–4.414; p = 0.029) significantly rise. HER-2 expression and anti-tumor therapy lines are statistically correlated with survivals. Conclusions Before the initiation of ICIs, enriched peripheral lymphocytes and poor neutrophils and NLR contribute to the prediction of survivals.
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    Evaluating Trastuzumab in the treatment of HER2 positive breast cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Jaques, Ryan; Xu, Sam; Matsakas, Antonios
    The transmembrane oncoprotein HER2 is encoded by ERBB2 gene and overexpressed in around 20% of invasive breast cancers. It can be specifically targeted by Trastuzumab (Herceptin ® ), a humanised IgG1 antibody. Trastuzumab has been regarded as one of the most effective therapeutic drugs targeted to HER2 positive cancers. However, there are drawbacks, notably cardiotoxicity and resistance, which have raised awareness in clinical use. Therefore, understanding the mechanism of action is vital to establish improved therapeutic strategies. Here we evaluate Trastuzumab application in the treatment of HER2 positive breast cancer, focusing on its mechanistic actions and clinical effectiveness. Alternative therapies targeting the HER2 receptor and its downstream anomalies will also be discussed, as these could highlight further targets that could be key to improving clinical outcomes.
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    Expression feature and prognostic function of a novel immune checkpoint Siglec-15 in human colorectal cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Liang, Guodong; Zhou, Linyun; Fan, Yang; Ding, Run; Yang, Junrong; Xu, Li; Zhu, Yidan; Huang, Wen
    Background. Sialic acid-bound immuno-globulin lectin 15 (Siglec-15) plays an important role in the development of cancer. However, the association between Siglec-15 expression and clinicopathological characteristics of colorectal cancer (CRC) has not been fully investigated. Methods. In this present study, a number of bioinformatics analyses were performed to provide an overview and detailed characteristics of Siglec-15. Quantitative real-time polymerase chain reaction (qPCR), western blotting and immunohistochemistry analyses were conducted to characterize the expression of Siglec-15 in CRC. Kaplan-Meier survival and Cox regression analyses were performed to identify the prognostic parameters of CRC. Results. The results of bioinformatics analyses revealed the expression characteristics and prognostic roles of Siglec-15 in CRC. The data of qCPR, western blotting, and IHC analyses demonstrated that the expression of Siglec-15 in CRC tissues was significantly higher than that in non-cancerous tissues. Moreover, the expression level of Siglec-15 in CRC was significantly associated with lymph node metastasis (p=0.001), TNM stage (p=0.001), and overall survival (p=0.026). COX multi-factor analysis indicated that Siglec-15 expression (p=0.023) and tumor differentiation (p=0.003) were independent prognostic factors for CRC. Conclusions. Collectively, the data suggested that Siglec-15 expression may serve as a novel prognostic factor and Siglec-15 might be identified as an ideal candidate for immunotherapy in CRC treatment.
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    In vitro antigen-specific cytotoxic T cell response against esophageal carcinoma cells induced by HPV18E7-transfected dendritic cells
    (Murcia : F. Hernández, 2010) Wu, Lin; Yang, Wei; Chen, Lin-Xin; Chen, Shen-Ren; Zhang, Jin-Kun
    Human Papillomavirus (HPV)-associatedesophageal carcinoma (EC) is a high incidence tumorworldwide. Dendritic cell (DC)-based tumor vaccine isconsidered an alternative therapy to treat EC. Here wedeveloped a DC-based vaccine by transfecting cordblood CD34+stem cell-derived DC with HPV18E7gene, observed its biological characteristics and theantigen-specific T-cell cytotoxicity on EC cells inducedby HPV18E7-DC in vitro. Our results showed that 1)HPV18E7 gene transfer did not change the typicalmorphology of mature DC, 2) the representativephenotypes of mature DC (CD80, CD86, and CD83)were highly expressed in HPV18E7- DC (81.6%, 80.5%,and 86.6%, respectively), 3) the expression level of18E7 protein in HPV18E7-DC was 47.5%, and 4) thespecific cytotoxicity against EC cells was significantlyhigher than that in controls (p<0.01). This studyindicates the possibility of a DC-based immunotherapyin HPV-associated EC.
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    Pembrolizumab plus gemcitabine in the subset of triple-negative advanced breast cancer patients in the GEICAM/2015-04 (PANGEA-Breast) study
    (MDPI, 2021-10-29) Cruz-Merino, Luis de la; Gion, María; Cruz-Jurado, Josefina; Quiroga, Vanesa; Andrés, Raquel; Moreno, Fernando; Alonso-Romero, José Luis; Ramos, Manuel; Holgado, Esther; Cortés, Javier; López-Miranda, Elena; Henao-Carrasco, Fernando; Palazón-Carrión, Natalia; Rodríguez, Luz M.; Ceballos, Isaac; Casas, Maribel; Benito, Sara; Chiesa, Massimo; Bezares, Susana; Caballero, Rosalia; Jiménez-Cortegana, Carlos; Sánchez-Margalet, Víctor; Rojo, Federico; Medicina
    The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.
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    The immune microenvironment of cancer of the uterine cervix
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2024) Mastrogeorgiou, Michail; Chatzikalil, Elena; Theocharis, Stamatios; Papoudou-Bai, Alexandra; Péoc’h, Michel; Mobarki, Mousa; Karpathiou, Georgia
    While several treatment choices exist for cervical cancer, such as surgical therapy, chemotherapy, and radiotherapy, some patients will still show poor prognosis. HPV infection is a principal factor for cervical cancer development, from early inflammation to proliferation, angiogenesis, and neoplastic growth. While HPV T-cell responses exist, the tumor seems to evade the immune system upon its tolerance. The latter suggests the existence of a confluent tumor microenvironment responsible for the evasion tactics employed by the neoplasm. Therefore, novel biomarkers governing prognosis and treatment planning must be developed, with several studies tackling the significance of the tumor microenvironment in the genesis, development, proliferation, and overall response of cervical cancer during neoplastic processes. This review aims to analyze and contemplate the characteristics of the tumor microenvironment and its role in prognosis, progression, evasion, and invasion, including therapeutic outcome and overall survival.
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    Valoración de la respuesta a inmunoterapia tras provocación nasal alergéno específica valorada mediante rinometría acústica y cuestionario de síntomas en pacientes pediátricos con rinitis alérgica
    (Universidad de Murcia, 2024-11-08) Osuna García, Teresa; Bosch Giménez, Vicente María; Pastor Rosado, José; Escuela Internacional de Doctorado
    Introducción: La rinitis alérgica es un importante problema de salud pública. Es una enfermedad que disminuye la calidad de vida y puede producir múltiples morbilidades. El único tratamiento etiológico capaz de modificar la historia natural de esta enfermedad es la inmunoterapia. Hasta ahora, no existe ningún instrumento eficaz que permita evaluar la respuesta a la inmunoterapia de forma precoz. En este estudio, se propone la provocación nasal valorada por rinometría acústica, junto con un cuestionario de síntomas y consumo de medicación, como una herramienta útil para medir precozmente la eficacia de la inmunoterapia. Material y métodos: Estudio cuasiexperimental, prospectivo, descriptivo y analítico en 57 pacientes de edad pediátrica, diagnosticados de rinitis alérgica por ácaros, candidatos a tratamiento con inmunoterapia específica frente a ácaros. Se ha realizado la provocación nasal valorada por rinometría acústica junto con un cuestionario de síntomas antes del inicio de la inmunoterapia, a los 6 meses y al año de iniciarla, comparando posteriormente los resultados. Los datos fueron procesados con el paquete estadístico IBM SPSS Statistics 22.0 para Windows, y se realizó un análisis descriptivo y analítico de las variables. Resultados: En la provocación nasal, al comparar los volúmenes de la provocación nasal a concentración de ácaros 1:100 se produce una reducción del descenso de volumen con significación estadística a los 6 meses y al año de haber iniciado ITE. Al igual que encontramos una reducción de la sintomatología durante la provocación nasal con diferencias estadísticamente significativas tanto a concentración de ácaros 1:100 como 1:10. También se objetiva una mejoría clínica a los 6 meses y un año tras haber iniciado la inmunoterapia, traducida en una mejoría en la puntuación en todas las escalas clínicas, con diferencias estadísticamente significativas. Al correlacionar las diferentes herramientas utilizadas para evaluar la respuesta a inmunoterapia no encontramos correlación entre las variables objetivas, obtenidas de la provocación nasal con rinometría acústica, y las variables subjetivas, obtenidas de los cuestionarios de síntomas. Sin embargo, ambas son útiles utilizadas de manera independiente. Por último, se han comparado los resultados obtenidos en la provocación nasal valorada por rinometría y en los cuestionarios de síntomas en función del género, gravedad de la rinitis alérgica, presencia o no de asma bronquial y número de sensibilizaciones, sin encontrar diferencias estadísticamente significativas entre ambos grupos en la mayoría de los casos. Conclusiones: A la luz de nuestros resultados, podemos concluir que la provocación nasal con rinometría acústica y los cuestionarios de síntomas pueden ser herramientas útiles para evaluar la respuesta a inmunoterapia.