The understanding of the relationship between immunological responses and cancers, especially those related to HPV, has allowed for the study and development of therapeutic vaccines against these neoplasias. There is a growing number of studies about the composition and influence of the tumor microenvironment (TME) in the progression or establishment of the most varied types of cancer. Hence, it has been possible to structure immunotherapy approaches based on therapeutic vaccines that are even more specific and directed to components of TME and the immune response associated with tumors. Among these components are dendritic cells (DCs), which are the main professional antigen-presenting cells (APCs) already studied in therapy strategies for HPV-related cancers. On the other hand, tumor-associated macrophages are also potential targets since the profile present in tumor infiltrates, M1 or M2, influences the prognosis of some types of cancer. These two cell types can be targets for therapy or immunomodulation. In this context, our review aims to provide an overview of immunotherapy strategies for HPV-positive tumors, such as cervical and head and neck cancers, pointing to TME immune cells as promising targets for these approaches. This review also explores the potential of immunotherapy in cancer treatment, including checkpoint inhibitors, cytokine immunotherapies, immunotherapy vaccines, and cell therapies. Furthermore, it highlights the importance of understanding the TME and its effect on the design and achievement of immunotherapeutic methods.

Background: The rapid advancement of the pandemic caused by SARS-CoV-2 and its variants reinforced the importance of developing easy-to-edit vaccines with fast production, such as multi-epitope DNA vaccines. The present study aimed to construct a synthetic antigen multi-epitope SARS-CoV-2 to produce a DNA vaccine. Methods: A database of previously predicted Spike and Nucleocapsid protein epitopes was created, and these epitopes were analyzed for immunogenicity, conservation, population coverage, and molecular docking. Results: A synthetic antigen with 15 epitopes considered immunogenic, conserved even in the face of variants and that were able to anchor themselves in the appropriate HLA site, together had more than 90% worldwide coverage. A multi-epitope construct was developed with the sequences of these peptides separated from each other by linkers, cloned into the pVAX1 vector. This construct was evaluated in vivo as a DNA vaccine and elicited T CD4+ and T CD8+ cell expansion in the blood and spleen. In hematological analyses, there was an increase in lymphocytes, monocytes, and neutrophils between the two doses. Furthermore, based on histopathological analysis, the vaccines did not cause any damage to the organs analyzed. Conclusions: The present study generated a multi-epitope synthetic vaccine antigen capable of generating antibody-mediated and cellular immune responses.

In the last decades, technological advances for RNA manipulation enabled and expanded its application in vaccine development. This approach comprises synthetic single-stranded mRNA molecules that direct the translation of the antigen responsible for activating the desired immune response. The success of RNA vaccines depends on the delivery vehicle. Among the systems, yeasts emerge as a new approach, already employed to deliver protein antigens, with efficacy demonstrated through preclinical and clinical trials. β-glucans and mannans in their walls are responsible for the adjuvant property of this system. Yeast β-glucan capsules, microparticles, and nanoparticles can modulate immune responses and have a high capacity to carry nucleic acids, with bioavailability upon oral immunization and targeting to receptors present in antigen-presenting cells (APCs). In addition, yeasts are suitable vehicles for the protection and specific delivery of therapeutic vaccines based on RNAi. Compared to protein antigens, the use of yeast for DNA or RNA vaccine delivery is less established and has fewer studies, most of them in the preclinical phase. Here, we present an overview of the attributes of yeast or its derivatives for the delivery of RNA-based vaccines, discussing the current challenges and prospects of this promising strategy.

The development of effective vaccines requires a rational design that considers the interaction between antigens, their vectors, and the immune system in addition to the activation of pathways that induce a safe and specific immune response. The efficacy of a vaccine formulation depends on the nature of the antigen, the protection offered by the delivery system, the ability to potentiate the immune response, and the precise release of the immunogen. Carrier systems such as lipid nanoparticles, polymers, exosomes, and microorganisms can be functionalized by chemical, physical, or biological methods to generate selective and improved biodistribution profiles. These methods enhance interaction with target cells, thereby improving immunological efficacy. The conjugation of specific ligands or the modification of parameters such as shape, charge, and size of vectors can enhance the specificity, stability, and efficiency of antigen transport to cellular compartments, thereby facilitating a robust immune response. This study examines modifications in vaccine delivery systems, focusing on biomolecules and physicochemical changes that enhance antigen presentation. Additionally, we examine innovative methods, including microneedles, electroporation, and needle-free systems that show potential for enhancing the immune response.

Breast cancer risk factors include lifestyle, genetic–hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.