Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study

Pistillo, Maria Pia; Fontana, Vincenzo; Morabito, Anna; Dozin, Béatrice; Laurent, Stefania; Carosio, Roberta; Banelli, Barbara; Ferrero, Francesca; Spanó, Laura; Tanda, Enrica T.; Ferrucci, Pier Francesco; Martinoli, Chiara; Cocorocchio, Emilia; Guida, Michele; Tommasi, Stefania; Galitiis, Federica De; Pagani, Elena; Cappellini, Gian Carlo Antonini; Marchetti, Paolo; Quaglino, Pietro; Fava, Paolo; Osella‐Abate, Simona; Ascierto, Paolo A.; Capone, Mariaelena; Simeone, Ester; Romani, Massimo; Spagnolo, Francesco; Queirolo, Paola

doi:10.1007/s00262-018-2258-1

Cited by 73 publications

(60 citation statements)

References 39 publications

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“…Similarly, CTLA-4 has been found to be expressed on melanoma cells and to drive tumor formation [272]. An Italian study also found that serum CTLA-4 may serve as a novel biomarker in predicting favorable response to ipilimumab [273]. Timely identification of these markers is crucial for determining treatment for melanoma patients.…”

Section: Immune Checkpoint (Ctla-4 Pd-1 Pd-l1)mentioning

confidence: 99%

Current Molecular Markers of Melanoma and Treatment Targets

Yang

Oak

Slominski

et al. 2020

IJMS

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Melanoma is a deadly skin cancer that becomes especially difficult to treat after it metastasizes. Timely identification of melanoma is critical for effective therapy, but histopathologic diagnosis can frequently pose a significant challenge to this goal. Therefore, auxiliary diagnostic tools are imperative to facilitating prompt recognition of malignant lesions. Melanoma develops as result of a number of genetic mutations, with UV radiation often acting as a mutagenic risk factor. Novel methods of genetic testing have improved detection of these molecular alterations, which subsequently revealed important information for diagnosis and prognosis. Rapid detection of genetic alterations is also significant for choosing appropriate treatment and developing targeted therapies for melanoma. This review will delve into the understanding of various mutations and the implications they may pose for clinical decision making.

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Section: Immune Checkpoint (Ctla-4 Pd-1 Pd-l1)mentioning

confidence: 99%

Current Molecular Markers of Melanoma and Treatment Targets

Yang

Oak

Slominski

et al. 2020

IJMS

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“…Increased pretherapy serum CRP levels are associated with adverse prognosis both with regard to response to treatment and survival of cancer patients receiving immunotherapy [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ], but increased pretherapy CRP levels are also associated with an increased risk of immune-mediated adverse reactions, including severe cytokine release syndrome ( Table 5 ) [ 103 , 109 , 110 ]. An increase in CRP levels may also precede the clinical symptoms of cytokine release syndrome [ 111 ].…”

Section: The Use Of Proinflammatory Markers In Cancer Patients Witmentioning

confidence: 99%

Combined C-Reactive Protein and Novel Inflammatory Parameters as a Predictor in Cancer—What Can We Learn from the Hematological Experience?

Bruserud

Aarstad

Tvedt

2020

Cancers

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The acute phase reaction is a systemic response to acute or chronic inflammation. The serum level of C-reactive protein (CRP) is the only acute phase biomarker widely used in routine clinical practice, including its uses for prognostics and therapy monitoring in cancer patients. Although Interleukin 6 (IL6) is a main trigger of the acute phase reactions, a series of acute phase reactants can contribute (e.g., other members in IL6 family or IL1 subfamily, and tumor necrosis factor α). However, the experience from patients receiving intensive chemotherapy for hematological malignancies has shown that, besides CRP, other biomarkers (e.g., cytokines, soluble cytokine receptors, soluble adhesion molecules) also have altered systemic levels as a part of the acute phase reaction in these immunocompromised patients. Furthermore, CRP and white blood cell counts can serve as a dual prognostic predictor in solid tumors and hematological malignancies. Recent studies also suggest that biomarker profiles as well as alternative inflammatory mediators should be further developed to optimize the predictive utility in cancer patients. Finally, the experience from allogeneic stem cell transplantation suggests that selected acute phase reactants together with specific markers of organ damages are useful for predicting or diagnosing graft versus host disease. Acute phase proteins may also be useful to identify patients (at risk of) developing severe immune-mediated toxicity after anticancer immunotherapy. To conclude, future studies of acute phase predictors in human malignancies should not only investigate the conventional inflammatory mediators (e.g., CRP, white blood cell counts) but also combinations of novel inflammatory parameters with specific markers of organ damages.

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“…As a CTLA-4 receptor form, sCTLA-4 plays an important role in inhibitory regulation of T-cell-mediated immune response [ 94 , 95 ] and presents a predictive value in ipilimumab melanoma therapy. In two independent reports, high pre-treatment sCTLA-4 concentration was associated with a lower death rate and a favorable clinical outcome in melanoma patients receiving ipilimumab treatment [ 96 , 97 ].…”

Section: Predictive Biomarkers Related To the Host Immune Systemmentioning

confidence: 99%

The Tumor and Host Immune Signature, and the Gut Microbiota as Predictive Biomarkers for Immune Checkpoint Inhibitor Response in Melanoma Patients

Tomela

Pietrzak

Schmidt

et al. 2020

Life

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There are various melanoma treatment strategies that are based on immunological responses, among which immune checkpoint inhibitors (ICI) are relatively novel form. Nowadays, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies represent a standard treatment for metastatic melanoma. Although there are remarkable curative effects in responders to ICI therapy, up to 70% of melanoma patients show resistance to this treatment. This low response rate is caused by innate as well as acquired resistance, and some aspects of treatment resistance are still unknown. Growing evidence shows that gut microbiota and bacterial metabolites, such as short-chain fatty acids (SCFAs), affect the efficacy of immunotherapy. Various bacterial species have been indicated as potential biomarkers of anti-PD-1 or anti-CTLA-4 therapy efficacy in melanoma, next to biomarkers related to molecular and genetic tumor characteristics or the host immunological response, which are detected in patients’ blood. Here, we review the current status of biomarkers of response to ICI melanoma therapies, their pre-treatment predictive values, and their utility as on-treatment monitoring tools in order to select a relevant personalized therapy on the basis of probability of the best clinical outcome.

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Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study

Cited by 73 publications

References 39 publications

Current Molecular Markers of Melanoma and Treatment Targets

Current Molecular Markers of Melanoma and Treatment Targets

Combined C-Reactive Protein and Novel Inflammatory Parameters as a Predictor in Cancer—What Can We Learn from the Hematological Experience?

The Tumor and Host Immune Signature, and the Gut Microbiota as Predictive Biomarkers for Immune Checkpoint Inhibitor Response in Melanoma Patients

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