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Plasma, the fourth state of matter could be artificially generated at room temperature under atmospheric pressure − termed as cold atmospheric plasma (CAP). The reactive oxygen and nitrogen radicals emanated during plasma discharge accord manifold applications in medicine and have proven clinical applications in cancer treatment, dentistry, and dermatology. Developments in the field termed “Plasma medicine” has inclined research toward its prospects in immunotherapy. Controlled generation of reactive oxygen and nitrogen radicals during plasma formation produces oxidative stress on tissue of concern, selectively and activates a number of cytological and molecular reactions, triggering immunological response. Plasma treatment induces immunogenic cell death (ICD) in tumor cells and elicits enhanced adaptive and systemic immune response with memory cells, conferring better defense to cancer. HIV inactivation, reduced viral replication, reversal of latency in HIV-infected cells, and augmented infected cell opsonization has been observed with CAP treatment. Plasma-treated medium has shown to deactivate  Herpes simplex  virus (HSV-1) in human corneal explants and epithelial cells, and lessen the severity of herpes simplex keratitis. Perception of cellular changes that triggers innate and adaptive immune response during CAP treatment is quintessential for understanding and expansion of research in this arena. This review mentions the inimitable properties of plasma that makes it a safe and sensitive immunotherapeutic tool. The methods of plasma generation relied for the purpose are elucidated. The cellular mechanism of immunological stimulation in cancer, HIV, and keratitis during CAP treatment is detailed. The future prospects and challenges are briefly addressed.HighlightsReactive oxygen and nitrogen radicals produced by cold atmospheric plasma (CAP) triggers oxidative stress in exposed cells.Cells in oxidative stress incite immunological response that could be suitably manipulated for immunotherapy.The role of reactive radicals and methods of plasma generation for immunotherapy is elucidated.The cellular and molecular cascade of reactions leading to immunological cell death in cancer cells is detailed.The mechanism of HIV inactivation and reduced infection; further, deactivation of HSV in Herpes keratitis in intact human corneal explants is also described. Reactive oxygen and nitrogen radicals produced by cold atmospheric plasma (CAP) triggers oxidative stress in exposed cells. Cells in oxidative stress incite immunological response that could be suitably manipulated for immunotherapy. The role of reactive radicals and methods of plasma generation for immunotherapy is elucidated. The cellular and molecular cascade of reactions leading to immunological cell death in cancer cells is detailed. The mechanism of HIV inactivation and reduced infection; further, deactivation of HSV in Herpes keratitis in intact human corneal explants is also described.

Cold atmospheric plasma-induced oxidative stress and ensuing immunological response – a Neo-Vista in immunotherapy