Immunotherapy using Regulatory T Cells in Cancer Suggests More Flavors of Hypersensitivity Type IV

Abstract

Regulatory T cells (Tregs) profoundly affect tumor microenvironment and exert dominant suppression over antitumor immunity in response to self-antigen expressed by tumor. Immunotherapy targeting Tregs lead to a significant improvement in antitumor immunity. Intradermal injection of tumor antigen results in negative delayed-type hypersensitivity (DTH) type IV. However, anti-Tregs treatment/use of adjuvant along with tumor antigens turns DTH to positive. Considering Tregs as the earliest tumor sensor/responders, tumor can be regarded as Treg-mediated type IV hypersensitivity and negative DTH to tumor antigen is due to anti-inflammatory action of Tregs to tumor antigens at the injection site. Such a view would help us in basic and clinical situations to testify a candidate vaccine via dermal administration and evaluation of Treg proportion at injection site.

Helper T cell subsets: Development, function and clinical role in hypersensitivity reactions in the modern perspective

“…The signalling crosstalk between other immune cells and T helper cells highlights the significance in studying immunomodulation in hypersensitivities. For example, Treg is responsible for modulating inflammatory responses in delayed-type hypersensitivities [ 117 ]. They possess immunosuppressive properties, such as suppressing the production of proinflammatory cytokines by interacting with helper T cells [ 117 , 118 ].…”

“…For example, Treg is responsible for modulating inflammatory responses in delayed-type hypersensitivities [ 117 ]. They possess immunosuppressive properties, such as suppressing the production of proinflammatory cytokines by interacting with helper T cells [ 117 , 118 ]. Specifically, Treg was found to be the key regulator of CD4 + helper T cells as they suppress the production of proinflammatory cytokines such as IL-1β, IL-6 and IL-12, potentially via the CD25 signalling axis [ 119 , 120 ].…”