Circulating inflammatory proteins associate with response to immune checkpoint inhibition therapy in patients with advanced melanoma

Rossi, Niccolò; Lee, Karla A.; Bermudez, Maria; Visconti, Alessia; Thomas, Andrew Maltez; Bolte, Laura A; Björk, Johannes; Ruijter, Laura Kist de; Newton-Bishop, Julia; Harland, Mark; Shaw, Heather; Harries, Mark; Sacco, Joseph J.; Board, Ruth; Lorigan, Paul; Vries, Elisabeth G.E. de; Segata, Nicola; Taams, Leonie S.; Papa, Sophie; Spector, Tim D.; Nathan, Paul; Weersma, Rinse K.; Hospers, Geke A.P.; Fehrmann, Rudolf S.N.; Bataille, Véronique; Falchi, Mario

doi:10.1016/j.ebiom.2022.104235

Cited by 15 publications

(11 citation statements)

References 40 publications

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“…Furthermore, analysing cytokine values in LDH− and LDH+MM patients we show that LDH+ patients have statistically significant higher values of IL-6, as well as IL-8 compared with LDH- patients. Rossi et al 22 also observed higher pretreatment levels of IL-6 among advanced melanoma patients with elevated LDH compared with patients with normal LDH values.…”

Section: Discussionmentioning

confidence: 89%

“…Since the onset of application of ICIs, several studies have investigated the association between baseline IL-6 level and response to therapy. In this sense, elevated pretreatment IL-6 levels have been associated with reduced ICI response rate in MM patients,22 27 28 as well as in non-small-cell lung cancer (NSCLC) patients 30–32. However, Yamazaki et al 33 have shown that responders (CR/PR) treated with nivolumab had remarkably higher level of pretreatment IL-6 than non-responders in 35 advanced BRAFwt, but also BRAF mutated MM patients.…”

Section: Discussionmentioning

confidence: 99%

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Circulating IL-6 is associated with disease progression in BRAFwt metastatic melanoma patients receiving anti-PD-1 therapy

et al. 2023

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AimsDespite efficacy of anti-PD-1 blockade in treatment of metastatic melanoma (MM), many patients achieve rapid disease progression (DP). Therefore, the aim of this study is to better define biomarkers for DP by analysing levels of circulating cytokines TGF-β, IFN-γ, IL-6, IL-8 and IL-10 in MM patients prior to anti-PD-1 therapy.MethodsCytokine levels were evaluated before therapy with pembrolizumab in peripheral blood of BRAF wild-type (wt) MM patients by ELISA method.ResultsIn this study, we give pretherapy levels for circulating TGF-β, IFN-γ, IL-6, IL-8 and IL-10 in BRAFwt MM patients and analyse them according to metastasis stage (M1a+M1 b, M1c, M1d groups), lactate dehydrogenase (LDH) level and occurrence of DP. Increased IL-6 level was found in M1d group (central nervous system metastasis), while LDH+patients (LDH ≥460 IU/L) have increased IL-6 and IL-8 values that correlate with LDH level. Also, IL-6 correlates with C reactive protein values. Furthermore, patients with DP have significantly higher IL-6 level compared with non-DP patients. Conversely, the other analysed cytokines are similar in investigated groups of MM patients. By receiver operating characteristics curve analysis, pretherapy IL-6 level was found to be a biomarker for the occurrence of DP with cut-off value of 3.02 pg/mL. Patients in M1d stage are prevalent in the group with IL-6 ≥3.02 pg/mL that is characterised with reduced progression-free survival and higher pretherapy IL-8 and LDH.ConclusionThe evidence in this study implies that baseline IL-6 could be a biomarker of DP and poor prognosis in BRAFwt MM patients treated with pembrolizumab.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Circulating IL-6 is associated with disease progression in BRAFwt metastatic melanoma patients receiving anti-PD-1 therapy

et al. 2023

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“…The production of a variety of pro-inflammatory cytokines secreted by macrophages, T lymphocytes and B lymphocytes in the tumor microenvironment encourages the survival and growth of tumor cells (16). Studies have shown that melanoma often has noticeable inflammatory reactions in the histopathological examination, and skin inflammation significantly promotes the growth of melanoma (17)(18)(19). Inflammation is a potential biomarker for stratified immunotherapy and targeted therapy in patients with melanoma (20).…”

Section: Discussionmentioning

confidence: 99%

Low expression of SEMA4D as a potential predictive molecular marker of poor survival in patients with melanoma combined with liver cancer

et al. 2023

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This study explored the correlation between semaphorin 4D (SEMA4D) and the prognosis and survival time of patients with melanoma combined with liver cancer. A total of 272 patients were recruited, and clinical and follow-up data were recorded. The expression levels of SEMA4D and SEMA3B were determined. Pearson's χ 2 test and Spearman's rank correlation coefficient were used to analyze the relationship between prognosis and the assessed parameters of melanoma patients. Univariate and multivariate Logistic regression and Cox proportional risk regression analyses were used for further analysis. Additionally, receiver operating characteristic curve and survival curves of subjects were plotted. The Pearson's χ 2 test showed that the prognosis of melanoma patients was significantly correlated with age, tumor grade, and decreased SEMA4D expression. Additionally, Spearman's correlation coefficient analysis showed that age, tumor grade, and SEMA4D expression were significantly correlated with prognosis. Univariate logistic regression analysis showed that age and tumor grade, and SEMA4D expression, were significantly correlated with prognosis. Older patients, a higher tumor grade, and lower SEMA4D expression were associated with a poorer prognosis. Multivariate logistic regression analysis showed that older patients had a poorer prognosis, and patients with lower SEMA4D expression levels had a significantly worse prognosis than patients with higher SEMA4D expression levels. Kaplan-Meier analysis showed that the survival time of older patients was lower than that of the younger patients. The survival times of patients with lower SEMA4D expression levels were significantly lower than that of patients with higher SEMA4D expression levels. Multivariate Cox regression analysis showed that the survival time of older patients was lower than that of younger patients. The survival time of melanoma patients with low SEMA4D expression was significantly lower than that of patients with higher SEMA4D expression. SEMA4D was significantly associated with melanoma, and lower SEMA4D expression was associated with a poorer survival prognosis in melanoma patients.

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“…On the other hand, several serum growth factors and cytokines secreted by the tumor or immune cells have been found to act as predictive biomarkers to ICI in other neoplasia, such as interleukin-6 (IL-6), [22][23][24][25] monocyte chemotactic protein 2 (MCP-2) 25 and hepatocyte growth factor (HGF). 25,26 In our ICI cohort, interleukin-7 (IL-7) was a predictive biomarker, since patients having high levels of IL-7 had longer OS, which was not recapitulated in the chemotherapy cohort. Interleukin-7 (IL-7) is a growth factor with a central role in normal T cell development, survival and differentiation [27][28][29] but its role in neutrophil biology has attracted less attention.…”

Section: Discussionmentioning

confidence: 99%

Circulating low density neutrophils are associated with resistance to anti‐PD1 immunotherapy in squamous head and neck cancer

Arrazubi,

Goñi,

González‐Borja

et al. 2023

Head & Neck

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BackgroundIdentification of predictive biomarkers to Immune checkpoint inhibitors (ICIs) in head and neck cancer (HNSCC) is an unmet need.MethodsThis was a prospective observational study including 25 patients with HNSCC treated with immunotherapy or chemotherapy after a prior platinum‐based regimen. Low density neutrophils (LDNs) and serum markers were analyzed.ResultsIn the immunotherapy cohort, patients with high LDN levels had a shorter progression free survival (PFS) (1.8 months vs. 10.9 months; *p = 0.034). Also, progressors showed higher percentage of LDNs compared to non‐progressors although significance was not reached (mean 20.68% vs. 4.095%, p = 0.0875). These findings were not replicated in patients treated with chemotherapy. High levels of interleukin‐7 (IL7) were correlated with a significantly longer overall survival (OS) (13.47 months 3.51 vs. months, *p = 0.013).ConclusionsHigh baseline circulating LDNs and low IL7 could identify a subset of patients intrinsically refractory to ICIs as monotherapy in HNSCC.

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Circulating inflammatory proteins associate with response to immune checkpoint inhibition therapy in patients with advanced melanoma

Cited by 15 publications

References 40 publications

Circulating IL-6 is associated with disease progression in BRAFwt metastatic melanoma patients receiving anti-PD-1 therapy

Circulating IL-6 is associated with disease progression in BRAFwt metastatic melanoma patients receiving anti-PD-1 therapy

Low expression of SEMA4D as a potential predictive molecular marker of poor survival in patients with melanoma combined with liver cancer

Circulating low density neutrophils are associated with resistance to anti‐PD1 immunotherapy in squamous head and neck cancer

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