Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses

Although immune checkpoint inhibitors (ICIs), such as anti–programmed cell death protein–1 (PD-1), can deliver durable antitumor effects, most patients with cancer fail to respond. Recent studies suggest that ICI efficacy correlates with a higher load of tumor-specific neoantigens and development of vitiligo in patients with melanoma. Here, we report that patients with low melanoma neoantigen burdens who responded to ICI had tumors with higher expression of pigmentation-related genes. Moreover, expansion of peripheral blood CD8+ T cell populations specific for melanocyte antigens was observed only in patients who responded to anti–PD-1 therapy, suggesting that ICI can promote breakdown of tolerance toward tumor-lineage self-antigens. In a mouse model of poorly immunogenic melanomas, spreading of epitope recognition toward wild-type melanocyte antigens was associated with markedly improved anti–PD-1 efficacy in two independent approaches: introduction of neoantigens by ultraviolet (UV) B radiation mutagenesis or the therapeutic combination of ablative fractional photothermolysis plus imiquimod. Complete responses against UV mutation-bearing tumors after anti–PD-1 resulted in protection from subsequent engraftment of melanomas lacking any shared neoantigens, as well as pancreatic adenocarcinomas forcibly overexpressing melanocyte-lineage antigens. Our data demonstrate that somatic mutations are sufficient to provoke strong antitumor responses after checkpoint blockade, but long-term responses are not restricted to these putative neoantigens. Epitope spreading toward T cell recognition of wild-type tumor-lineage self-antigens represents a common pathway for successful response to ICI, which can be evoked in neoantigen-deficient tumors by combination therapy with ablative fractional photothermolysis and imiquimod.

On the Application of Fractional Photothermolysis to Oral Mucosa in Patients with Orthostatic Disorders in the Early Postoperative Period

Высокий уровень ортогнатической патологии у пациентов молодого возраста заставляет изыскивать новые пути по оптимизации реабилитационного лечения в раннем послеоперационном периоде. Данное исследование посвящено разработке нового метода физиотерапевтического лечения слизистых и дентальных тканей полости рта в раннем послеоперационном периоде. Статья отражает результаты применения фракционного фототермолиза у пациентов после ортогнатической хирургии. Акцент делается на дентофасциальные деформации лица, жалобы больных и изменения в психологическом статусе в динамике применения инновационного метода физиотерапии в раннем послеоперационном периоде.

Apparatus methods in complex treatment of patients with atrophic scars

Atrophic scars are a common pathology that can have a negative impact on the patient’s quality of life. Methods for correcting atrophic scars include chemical peels, dermabrasion, ablative or non-ablative laser resurfacing, filler insertion, and surgical techniques. Depending on the type and severity of the scar, an individual approach is required to obtain satisfactory results. Material and methods. The study included 32 patients with atrophic scars. Depending on the therapy, the patients were divided into two groups in which they received microneedle radiofrequency therapy or fractional photothermolysis. The effectiveness of the methods of therapy was assessed using laser doppler fluometry and ultrasound scanning. Research results. The RF microneedle method and fractional photothermolysis have a positive effect on the epidermal-dermal structure of the skin, which is expressed in the approximation of the acoustic density and thickness of the epidermis and dermis to normal values, and also improve microcirculation. When analyzing the results of correction of atrophic scars, more pronounced positive dynamics was observed after the application of RF microneedles.

Physiotherapy of cicatricial skin changes in the conditions of metabolic syndrome

The article analyzes the effectiveness of combined application of fractional photothermolysis and fermencol ultraphonophoresis against the background of metabolic syndrome in patients with cicatricial skin changes. It is shown that the efficiency of combined physiotherapy is reduced if it is performed against the background of metabolic syndrome. It is proved that the leading pathogenetic factors of the metabolic syndrome that reduce the therapeutic potential of physiotherapy procedures are insulin resistance and lipid metabolism disorders. It is found that the use of fractional photothermolysis and fermencol ultraphonophoresis does not affect significantly the main parameters of the metabolic syndrome in patients with or without metabolic syndrome. It is suggested that to increase the effectiveness of physiotherapy in patients with cicatricial skin changes in the presence of disorders of carbohydrate and lipid metabolism, provoked by the development of insulin resistance, additional use of therapeutic factors used to correct metabolic disorders is necessary.