RESUMO
Immunotherapy has meant a great scientific advance in the treatment of cancer in recent years, being considered as the therapeutic cornerstone of some neoplasms. However, in some types of cancer only a fraction of patients achieve benefit, posing the challenges and limitations that lead us to the need to understand the complexity of tumor biology, the microenvironment and the responsiveness of each agent. The results currently exceed what was achieved by conventional chemotherapy, although it is not yet possible to determine whether these responses are lasting or represent cure. In this review, a broad approach to immunotherapy in cancer is proposed, from the basics to its clinical application, a discovery that was awarded the Nobel Prize in Medicine in 2018.
La inmunoterapia ha significado un gran avance científico en el tratamiento del cáncer en los últimos años, siendo considerada como la piedra angular terapéutica de algunas neoplasias. Sin embargo, en algunos tipos de cáncer sólo una fracción de pacientes alcanza beneficio, planteando los desafíos y limi tantes que nos llevan a la necesidad de entender la complejidad de la biología tumoral, el microambiente tumoral y la capacidad de respuesta de cada agente. Los resultados superan actualmente lo alcanzado por la quimioterapia convencional, aunque aún no se puede precisar si estas respuestas son duraderas o representan curación. En la presente revisión, se propone un enfoque amplio sobre la inmunoterapia en cáncer, desde los conceptos básicos hasta su aplicación clínica, descubrimiento que fue galardonado con el Premio Nobel de Medicina en el 2018.
Assuntos
Imunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Prêmio NobelRESUMO
RESUMEN La inmunoterapia ha significado un gran avance científico en el tratamiento del cáncer en los últimos años, siendo considerada como la piedra angular terapéutica de algunas neoplasias. Sin embargo, en algunos tipos de cáncer sólo una fracción de pacientes alcanza beneficio, planteando los desafíos y limi tantes que nos llevan a la necesidad de entender la complejidad de la biología tumoral, el microambiente tumoral y la capacidad de respuesta de cada agente. Los resultados superan actualmente lo alcanzado por la quimioterapia convencional, aunque aún no se puede precisar si estas respuestas son duraderas o representan curación. En la presente revisión, se propone un enfoque amplio sobre la inmunoterapia en cáncer, desde los conceptos básicos hasta su aplicación clínica, descubrimiento que fue galardonado con el Premio Nobel de Medicina en el 2018.
ABSTRACT Immunotherapy has meant a great scientific advance in the treatment of cancer in recent years, being considered as the therapeutic cornerstone of some neoplasms. However, in some types of cancer only a fraction of patients achieve benefit, posing the challenges and limitations that lead us to the need to understand the complexity of tumor biology, the microenvironment and the responsiveness of each agent. The results currently exceed what was achieved by conventional chemotherapy, although it is not yet possible to determine whether these responses are lasting or represent cure. In this review, a broad approach to immunotherapy in cancer is proposed, from the basics to its clinical application, a discovery that was awarded the Nobel Prize in Medicine in 2018.
Assuntos
Humanos , Imunoterapia , Neoplasias , Neoplasias/terapia , Prêmio NobelRESUMO
El desarrollo tecnológico de las últimas dos décadas aplicado a la investigación científica preclínica y clínica, ha permitido expandir significativamente los conocimientos acerca de la biología de las células neoplásicas. La caracterización de las alteraciones genéticas y epigenéticas que sustentan la carcinogénesis, la subclasificación molecular de los tumores, la comprensión de las interacciones que establecen las células neoplásicas con otras poblaciones celulares en el microambiente tumoral, así como la descripción de las bases moleculares que permiten explicar la influencia de factores como ejercicio, la dieta y la composición de la microbiota en la progresión tumoral, han contribuido a sustentar la relevancia del tratamiento de precisión en cáncer. Este trabajo revisa los llamados sellos del cáncer y sus cualidades habilitantes, o sea, aquellas propiedades inherentes a las células neoplásicas que le permiten evadir los mecanismos intrínsecos y extrínsecos que controlan la carcinogénesis. Con este trabajo damos continuidad a la serie sobre inmunología del cáncer que iniciamos con la presentación de las bases moleculares y celulares de la respuesta inmune antitumoral y que, finalmente, abordará la manipulación de la relación entre el sistema inmune y las neoplasias como estrategia de terapia para el cáncer.
Technological advances applied to preclinical and clinical scientific research have significantly enabled the broadening of knowledge regarding neoplastic cells biology in the last two decades. The characterization of genetic and epigenetic alterations which are involved in carcinogenesis; the molecular subclassification of tumors; the understanding of normal and neoplastic cells interactions in the tumor microenvironment; and the description of molecular bases that explain the influence of factors such as exercise, diet and microbiota composition on cancer progression have contributed to support the importance of precision medicine in cancer. The present research reviews the so-called "hallmarks of cancer" and their "enabling characteristics", i.e. those properties inherent to cancer cells that allow to evade intrinsic and extrinsic mechanisms of carcinogenesis control. This paper is a follow-up review of studies on cancer immunology that started with the presentation of the molecular and cellular bases of the anti-tumoral immune response, and will eventually focus on the manipulation of the relationship between the immune system and malignancies as a cancer treatment strategy.
Assuntos
Humanos , Carcinogênese , Proteínas Oncogênicas , Microambiente TumoralRESUMO
OBJECTIVE: The target concept means not only an aberrant expression of a particular molecule in tumour tissues but also evidence of a clear therapeutic advantage, as a consequence of immune-intervention, in an antigen-positive relevant tumour model. Since we reported the presence of NGcGM3 ganglioside in human breast tumours years ago and though Phase I clinical trials of a ganglioside containing vaccine have been conducted, a definitive direct validation of this peculiar molecule as target for cancer immunotherapy has remained unperformed. METHODS: Two animal models were used: leghorn chickens and C57BL/6 mice. The murine 3LL-D122 cell line, the derived subcutaneous tumours and metastatic lung lesions were processed for gangliosides identification. Active immunotherapy experiments in the 3LL-D122 spontaneous lung metastasis model were performed with NGcGM3/VSSP vaccine prepared by conjugation of NGcGM3 with the outer membrane proteins of Neisseria meningitides. RESULTS: The 3LL-D122 Lewis lung carcinoma results were consistent with an increased expression of NGcGM3 from primary tumours to metastatic lesions, as observed in human breast cancer samples. Both vaccines, prepared with synthetic or natural-source-derived ganglioside, showed similar anti-tumour and immunogenicity profiles. Finally, a clear involvement of NK1.1(+) cells and CD8(+) T cells in the anti-metastatic effect elicited by the vaccine was manifested. CONCLUSIONS: While 'proof of concept' Phase II and III clinical trials with the NGcGM3/VSSP vaccine in cancer patients are currently ongoing these results reasonably sustain the validation of this peculiar ganglioside as a novel target for cancer immunotherapy.