Process of inflammation and complex interactions between immune and cancer cells within tumor microenvironment are known to drive and shape the outcome of the neoplastic disease. Recent studies increasingly show that ion channels can be used as potential targets to modulate immune response and to treat inflammatory disorders and cancer. The action of both innate and adaptive immune cells is tightly regulated by ionic signals provided by a network of distinct ion channels. TRPV1 channel, known as a capsaicin receptor, was recently documented to be expressed on the cells of the immune system but also aberrantly expressed in the several tumor types. It is activated by heat, protons, proinflammatory cytokines, and associated with pain and inflammation. TRPV1 channel is not only involved in calcium signaling fundamental for many cellular processes but also takes part in cell-environment crosstalk influencing cell behavior. Furthermore, in several studies, activation of TRPV1 by capsaicin was associated with anti-cancer effects. Therefore, TRPV1 provides a potential link between the process of inflammation, cancer and immunity, and offers new treatment possibilities. Nevertheless, in many cases, results regarding TRPV1 are contradictory and need further refinement. In this review we present the summary of the data related to the role of TRPV1 channel in the process of inflammation, cancer and immunity, limitations of the studies, and directions for future research.

We investigated the salinity dependent expression dynamics of 7 aquaporin paralogs (aqp1a, -3a, -7, -8ab, -10a, -10b and -11a) in several tissues of euryhaline Japanese medaka (Oryzias latipes). All paralogs except aqp7 and -10a had a broad tissue distribution and several were affected by salinity in both osmoregulatory and non-osmoregulatory tissues. In the intestine, aqp1a, -7, -8ab and -10a decreased upon seawater (SW)-acclimation, both when comparing long-term acclimated fish and during 1-3 days of the transition period (freshwater (FW)-to-SW and SW-to-FW). In the gill, aqp3a was lower and aqp10a higher in SW than in FW. In the kidney no aqps were affected by salinity. In the skin, aqp1a and -3a were lower in SW than in FW. In the liver aqp8ab and -10a were lower in SW than in FW. Further, 6 Na+,K+-ATPase α-subunit isoform transcripts were analyzed in the intestine but showed no consistent response to salinity, suggesting that water transport is not regulated at this level. In contrast, mRNA of the Na+,K+, 2Cl--cotransporter type-2 showed a strong increase in the intestine in SW compared to FW fish. Using custom made antibodies, we localized Aqp1a, -8ab and -10a proteins in the apical region of enterocytes of FW fish. Apical staining intensity strongly decreased, vanished or moved to sub apical regions, when fish were acclimated to SW, supporting the lower mRNA expression in SW. Western blots confirmed the decrease in Aqp1a and -10a protein in SW. The strong decrease in aquaporin expression in the intestine of SW fish is surprising and challenges the paradigm for transepithelial intestinal water absorption in SW fishes.

Background: Cancer continues to be the leading cause of mortality in high-income countries, necessitating the development of more precise and effective treatment modalities. Immunotherapy, specifically adoptive cell transfer of T cell receptor (TCR)-engineered T cells (TCR-T therapy), has shown promise in engaging the immune system for cancer treatment. One of the biggest challenges in the development of TCR-T therapies is the proper prediction of the pairing between TCRs and peptide-human leukocyte antigen (pHLAs). Modern computational immunology, using artificial intelligence (AI)-based platforms, provides the means to optimize the speed and accuracy of TCR screening and discovery. Objective: This study proposes an observational clinical trial protocol to collect patient samples and generate a database of pHLA:TCR sequences to aid the development of an AI-based platform for efficient selection of specific TCRs. Methods: The multicenter observational study, involving 8 participating hospitals, aims to enroll patients diagnosed with stage II, III, or IV colorectal cancer adenocarcinoma. Results: Patient recruitment has recently been completed, with 100 participants enrolled. Primary tumor tissue and peripheral blood samples have been obtained, and peripheral blood mononuclear cells have been isolated and cryopreserved. Nucleic acid extraction (DNA and RNA) has been performed in 86 cases. Additionally, 57 samples underwent whole exome sequencing to determine the presence of somatic mutations and RNA sequencing for gene expression profiling. Conclusions: The results of this study may have a significant impact on the treatment of patients with colorectal cancer. The comprehensive database of pHLA:TCR sequences generated through this observational clinical trial will facilitate the development of the AI-based platform for TCR selection. The results obtained thus far demonstrate successful patient recruitment and sample collection, laying the foundation for further analysis and the development of an innovative tool to expedite and enhance TCR selection for precision cancer treatments. Trial Registration: ClinicalTrials.gov NCT04994093; https://clinicaltrials.gov/ct2/show/NCT04994093 International Registered Report Identifier (IRRID): DERR1-10.2196/45872

Cancer immunotherapy is recently considered the most promising treatment for human patients with advanced tumors and could be effectively combined with conventional therapies such as chemotherapy or radiotherapy. Patients with hematological malignancies and melanoma have benefited greatly from immunotherapies such as, adoptive cell transfer therapy, experiencing durable remissions and prolonged survival. In the face of increasing enthusiasm for immunotherapy, particularly for the administration of tumor-specific T lymphocytes, the question arises whether this method could be employed to improve treatment outcomes for canine patients. It is warranted to determine whether veterinary clinical trials could support comparative oncology research and thus facilitate the development of new cell-based therapies for humans. Herein, we discuss adoptive transfer of T lymphocytes and lymphokine-activated cells for application in veterinary oncology, in the context of human medicine achievements. Furthermore, we discuss potential benefits of using domestic dog as a model for immunotherapy and its advantages for translational medicine. We also focus on an emerging genome-editing technology as a useful tool to improve a T cells’ phenotype.

Crosstalk between neoplastic and immune cells in the tumor microenvironment (TME) influences the progression of disease in human and canine cancer patients. Given that canine mammary tumors are a useful model to study breast cancer biology, we aimed to evaluate the expression of genes associated with T lymphocyte activity in benign, malignant, and metastatic canine mammary tumors. Interestingly, metastatic tumors exhibit increased expression of CXCR3, CCR2, IL-4, IL-12p40, and IL-17. In particular, we focused on IL-17, a key interleukin associated with the Th17 lymphocyte phenotype. Th17 cells have been shown to play a contradictory role in tumor immunity. Although IL-17 showed a high expression in the metastatic tumors, the expression of RORγt, a crucial transcription factor for Th17 differentiation was barely detected. We further investigated IL-17 expression using immunohistochemistry, through which we confirmed the increased expression of this interleukin in malignant and metastatic mammary tumors. Finally, we compared the plasma levels of IL-17 in healthy and malignant mammary tumor-bearing dogs using ELISA but found no differences between the groups. Our data indicate that the IL-17 in metastatic tumors may be produced by other cell types, but not by Th17 lymphocytes. Overall, our results broaden the available knowledge on the interactions in canine mammary tumors and provide insight into the development of new therapeutic strategies, with potential benefits for human immune oncology.