Targeting Tumor Metabolism: A New Challenge to Improve Immunotherapy

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: Feb. 22, 2018

Currently, a marked number of clinical trials on cancer treatment have revealed the success immunomodulatory therapies based immune checkpoint inhibitors that activate tumor-specific T cells. However, therapeutic efficacy immunotherapies is only restricted to small fraction patients. A deeper understanding key mechanisms generating an immunosuppressive tumor microenvironment (TME) remains major challenge for more effective antitumor immunity. There growing evidence TME supports inappropriate metabolic reprogramming dampens cell function, and therefore impacts response progression. Notably, characterized by lack crucial carbon sources critical function increased inhibitory signals. Here, we summarize basics intrinsic extrinsic remodeling checkpoints underlying competition between infiltrating cells nutrients metabolites. Intriguingly, upregulation programmed death-L1 cytotoxic lymphocyte-associated antigen 4 alters programme drives their exhaustion. In this context, targeting both metabolism can beneficially enhance or temper immunity in inhospitable markedly improve immunotherapies.

Language: Английский

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Cutaneous Immune-Related Adverse Events (irAEs) to Immune Checkpoint Inhibitors: A Dermatology Perspective on Management

Journal of Cutaneous Medicine and Surgery, Journal Year: 2020, Volume and Issue: 25(1), P. 59 - 76

Published: Aug. 3, 2020

Immune checkpoint inhibitors have proven to be efficacious for a broad spectrum of solid organ malignancies. These monoclonal antibodies lead cytotoxic T-cell activation and subsequent elimination cancer cells. However, they can also immune intolerance immune-related adverse event (irAEs) that are new specific these therapies. Cutaneous irAEs the most common, arising in up 34% patients on PD-1 43% 45% CTLA-4 inhibitors. The common skin manifestations include maculopapular eruption, pruritus, vitiligo-like lesions. A grading system has been proposed, which guides management cutaneous based percent body surface area (BSA) involved. may prompt clinicians reduce drug doses, add systemic steroids regiment, and/or discontinue lifesaving immunotherapy. Thus, goal is early identification concurrent minimize treatment interruptions. We emphasize here severity reaction should not graded BSA involvement alone, but rather nature primary pathology. For instance, eruptions rarely affect <30% often managed conservatively with skin-directed therapies, while Stevens-Johnson syndrome (SJS) affecting even 5% aggressively immunotherapy discontinued at once. There limited literature available studies present anecdotal evidence. review strategies provide recommendations psoriatic, immunobullous, maculopapular, lichenoid, acantholytic eruptions, vitiligo, alopecias, vasculitides, SJS/toxic epidermal necrolysis, other related toxicities.

Language: Английский

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Systemic Treatment of Melanoma

Published: March 19, 2024

Abstract Systemic therapy for melanoma patients has dramatically improved over the past decade. New treatment strategies have significantly ameliorated survival and prognosis of affected patients. The indication immune directed targeted therapies expanded can be considered both very early stages as well advanced disease. Ongoing challenges deal with reducing development primary secondary resistance to antitumoural drugs identifying useful biomarkers improving quality life Overall, aim cure metastatic become more tangible than ever before.

Language: Английский

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Prevalence of dermatological toxicities in patients with melanoma undergoing immunotherapy: Systematic review and meta-analysis

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(8), P. e0255716 - e0255716

Published: Aug. 6, 2021

Background Checkpoint inhibitors have revolutionized advanced melanoma care; however, their cutaneous side effects not been definitively elucidated. Objective To identify the prevalence of toxicity in patients with treated immune checkpoint as monotherapy and/or combination chemotherapy radiotherapy. Materials and methods We performed a systematic review meta-analysis, which encompassed both clinical trials observational studies describing dermatological toxicities inhibitors. The protocol was registered International Prospective Register Systematic Review under number CRD42018091915. searches were using CINAHL, Cochrane CENTRAL, LILACS, LIVIVO, PubMed, Scopus, Web Science databases. methodological quality evaluated JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data Results A total 9,802 articles identified final sample comprised 39 studies. drugs ipilimumab, tremelimumab, pembrolizumab, nivolumab. results suggest that most prevalent effect grade 1 2 pruritus (24%), followed by rash (21%) vitiligo (10%). Conclusion are pruritus, rash, vitiligo, they rated mostly grades adverse events. Remarkably, is commonly found PD-1

Language: Английский

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Lichenoide Arzneimittelreaktionen

Der Hautarzt, Journal Year: 2018, Volume and Issue: 69(2), P. 116 - 120

Published: Jan. 25, 2018

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Cutaneous Adverse Reactions of Anticancer Agents

Dermatologic Clinics, Journal Year: 2019, Volume and Issue: 37(4), P. 555 - 568

Published: July 27, 2019

Language: Английский

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Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti‐CTLA4 and anti‐PD1 combination immunotherapy: Incidence, management, and clinical benefit

Cancer, Journal Year: 2021, Volume and Issue: 128(5), P. 975 - 983

Published: Nov. 1, 2021

Background In response to the increased use of combination checkpoint inhibitors (CPIs) and resulting cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated CPIs characterize CAE features their clinical impact, correlation in other organs, tumor response. Methods Patients from authors' institutional database who received at least 1 dose ipilimumab either nivolumab or pembrolizumab between January 1, 2012, December 31, 2017, for stage IV unresectable III were identified. The time next treatment (TTNT) was calculated start CPI therapy death, development CAEs tested a time‐dependent Cox regression identify associations TTNT. Results Eighty‐one (52.3%) experienced total 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), pruritus without rash (8.7%). median times onset resolution 21 days (range, 0‐341 days) 50 1‐352 days), respectively. Most resolved after entered maintenance phase oral antihistamines topical steroids. discontinuation occurred 4 (2.6%) because 49 (31.6%) immune‐related events, 20 (12.9%) progression death. For definitively (n = 134; 86.5%), TTNT significantly longer than (hazard ratio, 0.567; 95% CI, 0.331‐0.972; P .039). Conclusions mostly reversible rarely required discontinuation. associated TTNT, suggested possible benefit.

Language: Английский

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Purified human anti-Tn and anti-T antibodies specifically recognize carcinoma tissues

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: May 30, 2019

Abstract Described in several epithelial cancer cells, Tn- (GalNAcα1-O-Ser/Thr) and T- (Galβ3GalNAcα1-O-Ser/Thr) antigens are examples of tumor-associated antigens. Increased expression T-antigens is associated with tumor invasion metastasis, patients high concentration anti-Tn anti-T antibodies have a more benign evolution pathology. Asialofetuin (ASF) ovine submaxillary mucin (OSM) two glycoproteins that expose Tn-antigen, respectively. In this work, using ASF or OSM we affinity-purified from normal human plasma tested their ability to specifically recognize tissues. Whereas purified (purity degree increase 127-fold, 22% recovery) were mainly IgG, for enhancement 125-fold, 26% yield) the IgM fraction was predominant over IgG one. IgG2 subclass significantly enriched both antibody samples. Purified did not bind tissue (0/42), although recognized malignant tissues different origin such as colon carcinoma (11/77 by anti-Tn; 7/79 anti-T), breast (10/23 7/23 kidney (45/51 42/51 anti-T). Our results suggest potential anti-tumor therapeutic agents; restoring levels sera could positively affect pathologies.

Language: Английский

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Adjuvant and Neoadjuvant Therapeutics for the Treatment of Cutaneous Melanoma

Clinics in Plastic Surgery, Journal Year: 2021, Volume and Issue: 48(4), P. 651 - 658

Published: Aug. 18, 2021

Language: Английский

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Nivolumab‐induced plaque morphea in a malign melanoma patient

Journal of Cosmetic Dermatology, Journal Year: 2020, Volume and Issue: 20(8), P. 2645 - 2647

Published: Dec. 24, 2020

Nivolumab is one of the targeted cancer therapy agent that acts to increase immune responses by inhibition antiprogrammed-death-receptor 1, which check points response. can be used treat malign melanoma, lung, renal, head and neck, colorectal, hepatocellular cancers, special cases Hodgkin lymphoma.We aimed report a rarer cutaneous side effect nivolumab because increasing uses this in various treatments.We present 48-year-old female, metastatic melanoma patient who developed plaque morphea lesion without any systemic involvement during treatment. Plaque responded well use topical corticosteroid calcipotriol.Numerous effects associated with have been reported literature. The most common are maculopapular rash, pruritus, vitiligo. Morphea disorders from spectrum due PD-1 inhibitors literature are; morphea, sclerodermoid changes, eosinophilic fasciitis, lichen sclerosis.Patients treated may examined carefully terms scleroderma-like conditions although they not as other effects.

Language: Английский

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