Serum concentrations of HGF are correlated with response to anti-PD-1 antibody therapy in patients with metastatic melanoma

Kubo, Yosuke; Fukushima, Satoshi; Inamori, Yukiko; Tsuruta, Mina; Egashira, Sho; Yamada‐Kanazawa, Saori; Tokuzumi, Aki; Miyashita, Azusa; Aoi, Jun; Kajihara, Ikko; Tomita, Yusuke; Wakamatsu, Kazumasa; Jinnin, Masatoshi; Ihn, Hironobu

doi:10.1016/j.jdermsci.2018.10.001

Cited by 21 publications

(15 citation statements)

References 24 publications

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“…The non-responders had elevated serum concentrations of HGF compared with the responders (p = 0.00124). On the other hand, the serum concentrations of 5SCD and LDH also followed this tendency [101]. 5SCD may be superior to LDH in predicting the treatment response and disease progression in patients receiving immune checkpoint inhibitors [82].…”

Section: Usefulness Of 5scd In Monitoring Treatments For Melanomamentioning

confidence: 84%

“…In actual clinical practice, it seems better to use a combination of LDH and 5SCD. In order to investigate whether the serum concentration of hepatocyte growth factor (HGF) can be used as a biomarker of anti-programmed cell death protein (PD)-1 antibodies, Kubo et al In order to investigate whether the serum concentration of hepatocyte growth factor (HGF) can be used as a biomarker of anti-programmed cell death protein (PD)-1 antibodies, Kubo et al compared serum HGF concentrations in responder and non-responders to anti-PD-1 antibody treatment [101]. HGF was suggested to serve as a paracrine mediator that controls placental development and growth [102].…”

Section: Usefulness Of 5scd In Monitoring Treatments For Melanomamentioning

confidence: 99%

“…In contrast, serum LDH levels at the upper limit of the normal range did not exhibit such changes. compared serum HGF concentrations in responder and non-responders to anti-PD-1 antibody treatment [101]. HGF was suggested to serve as a paracrine mediator that controls placental development and growth [102].…”

Section: Usefulness Of 5scd In Monitoring Treatments For Melanomamentioning

confidence: 99%

“…The serum concentration of hepatocyte growth factor (HGF) (A), LDH (B) and 5SCD (C) in non-responders and in responders to anti-PD-1 therapy. ThisFigure wasmodified with the consent of authors (Kubo et al[101]). …”

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confidence: 99%

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Significance of 5-S-Cysteinyldopa as a Marker for Melanoma

Wakamatsu

Fukushima

Minagawa

et al. 2020

IJMS

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Melanoma is one of the most lethal and malignant cancers and its incidence is increasing worldwide, and Japan is not an exception. Although there are numerous therapeutic options for melanoma, the prognosis is still poor once it has metastasized. The main concern after removal of a primary melanoma is whether it has metastasized, and early detection of metastatic melanoma would be effective in improving the prognosis of patients. Thus, it is very important to identify reliable methods to detect metastases as early as possible. Although many prognostic biomarkers (mainly for metastases) of melanoma have been reported, there are very few effective for an early diagnosis. Serum and urinary biomarkers for melanoma diagnosis have especially received great interest because of the relative ease of sample collection and handling. Several serum and urinary biomarkers appear to have significant potential both as prognostic indicators and as targets for future therapeutic methods, but still there are no efficient serum and urinary biomarkers for early detection, accurate diagnosis and prognosis, efficient monitoring of the disease and reliable prediction of survival and recurrence. Levels of 5-S-cysteinyldopa (5SCD) in the serum or urine as biomarkers of melanoma have been found to be significantly elevated earlier and to reflect melanoma progression better than physical examinations, laboratory tests and imaging techniques, such as scintigraphy and echography. With recent developments in the treatment of melanoma, studies reporting combinations of 5SCD levels and new applications for the treatment of melanoma are gradually increasing. This review summarizes the usefulness of 5SCD, the most widely used and well-known melanoma marker in the serum and urine, compares 5SCD and other useful markers, and finally its application to other fields.

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Section: Usefulness Of 5scd In Monitoring Treatments For Melanomamentioning

confidence: 84%

Section: Usefulness Of 5scd In Monitoring Treatments For Melanomamentioning

confidence: 99%

Section: Usefulness Of 5scd In Monitoring Treatments For Melanomamentioning

confidence: 99%

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confidence: 99%

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Significance of 5-S-Cysteinyldopa as a Marker for Melanoma

Wakamatsu

Fukushima

Minagawa

et al. 2020

IJMS

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“…B) . High serum concentrations of HGF have been correlated with the absence of response to anti‐PD‐1 in melanoma and HGF has been found to downregulate the expression or perforin . The reduction in secretion of SDF‐1α and HGF would suggest enhanced on‐treatment CD8 + TIL functionality.…”

Section: Resultsmentioning

confidence: 99%

Exposure to anti‐PD‐1 causes functional differences in tumor‐infiltrating lymphocytes in rare solid tumors

Creasy

Forget

Singh³

et al. 2019

Eur J Immunol

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The pervasive use of therapeutic antibodies targeting programmed cell death protein 1 (PD-1) to boost anti-tumor immunity has positioned this approach to become the standard-of-care for some solid tumor malignancies. However, little is known as to how blockade of PD-1 may alter the function or phenotype of tumor-infiltrating lymphocytes (TIL). We used our ongoing Phase II clinical trial of pembrolizumab for patients with rare solid tumors from various types (NCT02721732) with matched core biopsies taken at baseline and after initial dose of anti-PD-1 (15-21 days post-dose) to elucidate this question. One fresh core needle biopsy was used to propagate TIL ex vivo to analyze phenotype and function using flow cytometry in both CD8 + and CD4 + TIL populations. An enriched CTLA-4 expression in the CD4 + TIL population was observed in TIL expanded from the on-treatment samples compared to TIL expanded from the matched baseline (n = 22, p = 0.0007) but was not observed in patients who experienced tumor regression. Impact on functionality was evaluated by measuring secretion of 65 soluble factors by expanded TIL from 26 patients at baseline and on-treatment. The CD8 + TIL population demonstrated a diminished cytokine secretion profile post-pembrolizumab. Overall, our study assesses the ramifications of one dose of anti-PD-1 on TIL in rare solid tumor types.Keywords: Anti-PD-1 r CTLA-4 r Immunotherapy r Rare solid tumors r TIL Additional supporting information may be found online in the Supporting Information section at the end of the article.

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Serum cytokines and creatinine/cystatin C ratio as prognostic biomarkers in advanced cancer patients treated with anti-PD-1/PD-L1 therapy

Jin,

Liu,

et al. 2024

Support Care Cancer

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Objective Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. Methods The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. Results Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. Conclusions Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.

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Serum concentrations of HGF are correlated with response to anti-PD-1 antibody therapy in patients with metastatic melanoma

Cited by 21 publications

References 24 publications

Significance of 5-S-Cysteinyldopa as a Marker for Melanoma

Significance of 5-S-Cysteinyldopa as a Marker for Melanoma

Exposure to anti‐PD‐1 causes functional differences in tumor‐infiltrating lymphocytes in rare solid tumors

Serum cytokines and creatinine/cystatin C ratio as prognostic biomarkers in advanced cancer patients treated with anti-PD-1/PD-L1 therapy

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