RESUMEN
The tumor microenvironment that refers to the tumor's surroundings is a key modulator of tumor growth and invasion. The tumor-derived signals are known to downregulate the anti-tumor effects of the effector cells present in the TME. Thus, the cross-talk between the tumor cells with the surrounding immune cells helps in evading the tumor surveillance as well as aiding in tumor growth and proliferation. Hence, knowledge regarding the effects of drugs/compound on the tumor-stromal interactions is gaining importance. In the present study, the effects of jacalin, a dietary lectin on the proliferation and cytokine production of peripheral blood mononuclear cells (PBMCs), are investigated. Jacalin was shown to act as a mitogen of PBMCs, the key cytokine secreting immune cells. Also, jacalin initially induced increased mRNA expression of pro-inflammatory cytokine IFN-γ; however, prolonged stimulation of PBMCs resulted in increased expression of anti-inflammatory cytokine, mainly TGF-ß. Furthermore, 6 h jacalin prestimulated PBMCs (Jac-PBMCs) were shown to inhibit HeLa cell proliferation while 24 h Jac-PBMCs were found to favor tumor growth. Thus, it may be postulated that while jacalin initially polarizes the PBMCs to hinder the tumor growth, after a stipulated time point, interaction of jacalin with PBMCs can lead to an immunosuppressive TME that may probably assist in tumor growth and progression.
Asunto(s)
Artocarpus/química , Agentes Inmunomoduladores/farmacología , Leucocitos Mononucleares/inmunología , Lectinas de Plantas/farmacología , Células HeLa , Humanos , Agentes Inmunomoduladores/química , Interferón gamma/inmunología , Células K562 , Lectinas de Plantas/química , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
In recent years, studies have begun to explore the immune involvement in head and neck tumors. Advanced stage head and neck squamous cell carcinoma (HNSCC) has a poor prognosis with low survival rates with high level of immune infiltrates. Tregs (regulatory T cells) play a crucial role in constructing an immunosuppressive tumor microenvironment. In the present study, we highlighted specific Treg markers and its factors in HNSCC solid tumors and peripheral blood of cancer patients. By histopathology and immunofluorescence staining, we observed differential expression of CD4, CD25, Foxp3, Helios and Neuropilin-1. Further, we analyzed the expression of Foxp3, Helios, Neuropilin-1 and GARP by qPCR and flow cytometry in whole blood and found to be elevated in HNSCC patients in comparison with healthy donors. Additionally, IFN-γ, TGF-ß, IL-6, IL-2, IL-10 and TNF-α expressions were also found to be relatively increased in the head and neck cancer patients when compared with healthy donors. Our findings emphasize that Tregs may be involved in promoting tumor progression. Helios and Neuropilin-1 could be potent markers in identifying subsets of Tregs. Association of soluble factors could sculpture the activity of Tregs. With further research, Treg markers and its associated soluble factors could be employed to block Tregs trafficking to the tumor, thus enlightening a potential strategy for targeting human cancers.