Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2 are receptors that act in co-stimulatory and coinhibitory immune responses. Signaling the PD-1/PD-L1 or PD-L2 pathway is essential to regulate the inflammatory responses to infections, autoimmunity, and allergies, and it has been extensively studied in cancer. Allergic diseases include asthma, rhinoconjunctivitis, atopic dermatitis, drug allergy, and anaphylaxis. These overactive immune responses involve IgE-dependent activation and increased CD4+ T helper type 2 (Th2) lymphocytes. Recent studies have shown that PD-L1 and PD-L2 act to regulate T-cell activation and function. However, the main role of PD-1 and its ligands is to balance the immune response; however, the inflammatory process of allergic diseases is poorly understood. These immune checkpoint molecules can function as a brake or a kick-start to regulate the adaptive immune response. These findings suggest that PD-1 and its ligands may be a key factor in studying the exaggerated response in hypersensitivity reactions in allergies. This review summarizes the current understanding of the role of PD-1 and PD-L1 and PD-L2 pathway regulation in allergic diseases and how this immunomodulatory pathway is currently being targeted to develop novel therapeutic immunotherapy.

According to data from the U.S. National Cancer Institute, cancer is one of the leading causes of death worldwide with approximately 14 million new cases and 8.2 million cancer-related deaths in 2018. More than 60% of the new annual cases in the world occur in Africa, Asia, Central America, and South America, with 70% of cancer deaths in these regions. Breast cancer is the most common cancer in women, with 266,120 new cases in American women and an estimated 40,920 deaths for 2018. Approximately one in six women diagnosed with breast cancer will die in the coming years. Recently, novel therapeutic strategies have been implemented in the fight against breast cancer, including molecules able to block signaling pathways, an inhibitor of poly [ADP-ribose] polymerase (PARP), growth receptor blocker antibodies, or those that reactivate the immune system by inhibiting the activities of inhibitory receptors like cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death protein 1 (PD-1). However, novel targets include reactivating the Th1 immune response, changing tumor microenvironment, and co-activation of other components of the immune response such as natural killer cells and CD8+ T cells among others. In this article, we review advances in the treatment of breast cancer focused essentially on immunomodulatory drugs in targeted cancer therapy. Based on this knowledge, we formulate a proposal for the implementation of combined therapy using an extracorporeal immune response reactivation model and cytokines plus modulating antibodies for co-activation of the Th1- and natural killer cell (NK)-dependent immune response, either in situ or through autologous cell therapy. The implementation of “combination immunotherapy” is new hope in breast cancer treatment. Therefore, we consider the coordinated activation of each cell of the immune response that would probably produce better outcomes. Although more research is required, the results recently achieved by combination therapy suggest that for most, if not all, cancer patients, this tailored therapy may become a realistic approach in the near future.

Mast cells have been implicated in allergic diseases such as asthma, rhinitis, conjunctivitis, atopic dermatitis, urticaria, and anaphylaxis. However, it is now well established that they also fulfill critical roles in tissue homeostasis, repair, and defense. Despite considerable progress, their ontogeny, proliferation, and differentiation remain subjects of debate, as does their involvement in a wide spectrum of diseases, including cancer and cardiovascular disorders. What remains indisputable is their essential contribution to both innate and adaptive immune responses. Importantly, the activity of their effector molecules can elicit either protective or deleterious outcomes. A complete absence of mast cells (MCs) in humans would undoubtedly provide valuable insight into their fundamental role in immunity, much as neutropenia and agranulocytosis have historically clarified the functions of neutrophils. In this review, we provide a comprehensive overview of mast cell (MC) biology, emphasizing their functional diversity and pathogenic potential. Furthermore, we highlight emerging therapeutic strategies, particularly the use of inhibitors and monoclonal antibodies, which are reshaping current approaches to conditions such as allergy, mastocytosis, and related disorders.

Human parainfluenza virus type 1 (HPIV-1) is the most common cause of croup in infants. The aim of this study was to describe molecular mechanisms associated with IL-8 production during HPIV-1 infection and the role of viral replication in MAPK synthesis and activation. An in vitro model of HPIV-1 infection in the HEp-2 and A549 cell lines was used; a kinetic-based ELISA for IL-8 detection was also used, phosphorylation of the mitogen-activated protein kinases (MAPKs) was identified by Western blot analysis, and specific inhibitors for each kinase were used to identify which MAPK was involved. Inactivated viruses were used to assess whether viral replication is required for IL-8 production. Results revealed a gradual increase in IL-8 production at different selected times, when phosphorylation of MAPK was detected. The secretion of IL-8 in the two cell lines infected with the HPIV-1 is related to the phosphorylation of the MAPK as well as viral replication. Inhibition of p38 suppressed the secretion of IL-8 in the HEp-2 cells. No kinase activation was observed when viruses were inactivated.

Respiratory allergies affect humans worldwide, causing extensive morbidity and mortality. They include allergic rhinitis (AR), asthma, pollen food allergy syndrome (PFAS), aspirin-exacerbated respiratory disease (AERD), and nasal polyps (NPs). The study of respiratory allergic diseases requires new technologies for early and accurate diagnosis and treatment. Omics technologies provide the tools required to investigate DNA, RNA, proteins, and other molecular determinants. These technologies include genomics, transcriptomics, proteomics, and metabolomics. However, proteomics is one of the main approaches to studying allergic disorders’ pathophysiology. Proteins are used to indicate normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. In this field, the principal goal of proteomics has been to discover new proteins and use them in precision medicine. Multiple technologies have been applied to proteomics, but that most used for identifying, quantifying, and profiling proteins is mass spectrometry (MS). Over the last few years, proteomics has enabled the establishment of several proteins for diagnosing and treating respiratory allergic diseases.

Allergic diseases affect nearly 30% of people worldwide. There is a wide range of allergen sources, such as animal dander, food, venom, dust mites, and pollen. The skin prick test is the predominant technique used to identify allergenic sensitivity in vivo; the main problem is that it can be imprecise as many of the allergen extracts are made of mixtures of allergic and nonallergic components, making it difficult to identify the disease-eliciting allergen. An alternative to solve this problem is employing cellular models in vitro that may allow allergen identification, allergy diagnosis, and testing of novel potential compounds that can be used in immunotherapeutics. For example, rat basophilic leukemia (RBL) cells are a well-suited model for studying allergies. Unfortunately, cells generated from RBL cells are not commercially available. Therefore, we developed an RBL model with a degranulation gene reporter capable of recognizing human IgE involved in allergenic sensitivity using commercial plasmids. Employing this model, we successfully evaluated the capacity of union between IgE from allergic patients to allergenic proteins from Oleaceae tree pollen. This RBL cell model can be used as a diagnostic method for sensitivity to any allergens from different sources in vitro.