Immunological-based approaches for cancer therapy

The immunologic landscape of tumors has been continuously unveiled, providing a new look at the interactions between cancer cells and the immune system. Emerging tumor cells are constantly eliminated by the immune system, but some cells establish a long-term equilibrium phase leading to tumor immunoediting and, eventually, evasion. During this process, tumor cells tend to acquire more mutations. Bearing a high mutation burden leads to a greater number of neoantigens with the potential to initiate an immune response. Although many tumors evoke an immune response, tumor clearance by the immune system does not occur due to a suppressive tumor microenvironment. The mechanisms by which tumors achieve the ability to evade immunologic control vary. Understanding these differences is crucial for the improvement and application of new immune-based therapies. Much effort has been placed in developing in silico algorithms to predict tumor immunogenicity and to characterize the microenvironment via high-throughput sequencing and gene expression techniques. Each sequencing source, transcriptomics, and genomics yields a distinct level of data, helping to elucidate the tumor-based immune responses and guiding the fine-tuning of current and upcoming immune-based therapies. In this review, we explore some of the immunological concepts behind the new immunotherapies and the bioinformatic tools to study the immunological aspects of tumors, focusing on neoantigen determination and microenvironment deconvolution. We further discuss the immune-based therapies already in clinical use, those underway for future clinical application, the next steps in immunotherapy, and how the characterization of the tumor immune contexture can impact therapies aiming to promote or unleash immune-based tumor elimination.

Inmunoterapia del cáncer: Importancia de controlar la inmunosupresión / Cancer immunotherapy: Importance of overcoming immune suppression

Es cada vez mayor la evidencia experimental y clínica de que el sistema inmunitario interviene activamente en la patogénesis y el control de la progresión tumoral. Una respuesta antitumoral efectiva depende de la correcta interacción de varios componentes del sistema inmunitario, como las células presentadoras de antígeno y diferentes sub-poblaciones de linfocitos T. Sin embargo, los tumores malignos desarrollan numerosos mecanismos para evadir el reconocimiento y su eliminación por parte del sistema inmunitario. En esta revisión discutiremos algunos de esos mecanismos y posibles estrategias terapéuticas para contrarrestarlos.

Increasing evidence indicates that the immune system is involved in the control of tumor progression. Effective antitumor immune response depends on the interaction between several components of the immune system, including antigen-presenting cells and different T cell subsets. However, tumor cells develop a number of mechanisms to escape recognition and elimination by the immune system. In this review we discuss these mechanisms and address possible therapeutic approaches to overcome the immune suppression generated by tumors.

Dissecando os caminhos de escape do tumor: "uma questão de vida e morte?" / Dissecting the pathways of tumour escape: "a question of life and death?"

Apoptotic pathways are providing important saveguard mechanisms in protection from cancer by eliminating altered and often harmful cells. The disturbances of cell proliferation, differentiation and apoptosis are also found on specific signal-transduction pathways within the tumour cells and between these and the immune system. The article focuses attention on the evolution of the melanocytic naevi in the direction of a dysplastic or tumour cell. The determination of single molecules as prognostic parameters within cancer genesis seems to be problematic. New hopes are being placed on the treatment with TW-37, ABT-737 and TAT-Bim, which, to an extent, are able to support the programmed cell death. The clinical importance of these innovative therapies remains to be seen and should therefore, be viewed with considerable criticism.

Caminhos apoptóticos estão fornecendo importantes mecanismos de salvaguarda na proteção contra o câncer através da eliminação de células alteradas e freqüentemente nocivas.Os distúrbios de proliferação, diferenciação e apoptose celular são também encontrados nos caminhosespecíficos sinal-transdução dentro das células tumor e entre essas células e o sistema imunitário. O artigo foca na evolução da verruga conhecida como melanocytic naevi em direção a uma célula displasica ou célula tumor. A determinação de moléculas isoladas como parâmetros de prognóstico dentro da gênesis do câncer parece problemática. Novas esperanças estão sendo colocadas no tratamento com TW-37, ABT-737 e TAT-Bim, os quais, até certo ponto, são aptos a apoiar a morte celular programada (PCD). A importância clínica dessas terapias inovadoras permanece ainda a ser vista e devem, por essa razão, seremolhadas com considerável juízo crítico.