Cytokine Profiling of End Stage Cancer Patients Treated with Immunotherapy

Merlano, Marco; Abbona, Andrea; Paccagnella, Matteo; Falletta, Antonella; Granetto, Cristina; Ricci, Vincenzo; Fea, Elena; Denaro, Nerina; Ruatta, Fiorella; Merlotti, Anna; Bertetto, Oscar; Crosetto, Nicola; Galizia, Danilo; Basiricò, Marco; Gammaitoni, Loretta; Sangiolo, Dario; Garrone, Ornella

doi:10.3390/vaccines9030235

Cited by 3 publications

(3 citation statements)

References 35 publications

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“…Since the analysis pooled a small cohort of multiple cancer types, this conclusion needs to be interpreted with some caution. 20 A recent Mendelian randomisation study found that genetically predicted higher plasma levels of CCL2 increased the risk of developing PCa, which supports the concept of using CCL2 as a PCa biomarker. 21 However, gene variants causing a problematic increase in CCL2 plasma levels may be too rare to warrant the use of plasma CCL2 levels as a diagnostic biomarker.…”

Section: Discussionmentioning

confidence: 66%

Plasma Chemokine C-C Motif Ligand 2 as a Potential Biomarker for Prostate Cancer

Lund¹,

Pedersen²,

Feddersen³

et al. 2022

RRU

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Purpose Serum levels of the polypeptide chemokine C-C motif ligand 2 (CCL2) have previously shown potential as a prostate cancer diagnostic and prognostic biomarker. Plasma CCL2 levels may be superior to serum levels as a biomarker because of their potentially lower signal-to-noise ratio. Materials and Methods Before initiating a large comparative study of plasma and serum CCL2 levels, we performed a prospective, diagnostic pilot study Of 133 individuals from a clinically relevant population. CCL2 plasma levels were measured using a validated assay kit. Plasma was obtained independently of digital rectal examination. Results In this pilot study, we found no relationship between CCL2 plasma values and risk of proven prostate cancer, whereas previous studies found a strong diagnostic relationship between CCL2 serum values and prostate cancer. Conclusion Our contribution to the existing literature strengthens the idea that early in the pathological process, CCL2 mainly circulates in large, membrane-enclosed compartments, whereas plasma CCL2 levels increase markedly during disease progression. We conclude that whereas plasma CCL2 levels are not useful as a diagnostic measure, a ratio of CCL2 plasma to serum levels may prove useful as a marker of disease progression, which warrants further study.

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Section: Discussionmentioning

confidence: 66%

Plasma Chemokine C-C Motif Ligand 2 as a Potential Biomarker for Prostate Cancer

Lund¹,

Pedersen²,

Feddersen³

et al. 2022

RRU

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“…The 18 cytokines selected in our study are extensively included by other authors in panels aimed to identify prognostic/predictive biomarkers in other solid tumors [24,25]. Moreover, the same cytokines were tested in other cancers by our group, showing to be useful in identifying potential biomarkers [26,27].…”

Section: Discussionmentioning

confidence: 98%

Baseline Values of Circulating IL-6 and TGF-β Might Identify Patients with HNSCC Who Do Not Benefit from Nivolumab Treatment

Merlano,

Paccagnella,

Denaro

et al. 2023

Cancers

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Background: The immunotherapy of head and neck cancer induces a limited rate of long-term survivors at the cost of treating many patients exposed to toxicity without benefit, regardless of PD-L1 expression. The identification of better biomarkers is warranted. We analyzed a panel of cytokines, chemokines and growth factors, hereinafter all referred to as ‘cytokines’, as potential biomarkers in patients with head and neck cancer treated with nivolumab. Materials and methods: A total of 18 circulating cytokines were analyzed. Samples were gathered at baseline (T0) and after 3 courses of nivolumab (T1) in patients with relapsed/metastatic disease. The data extracted at T0 were linked to survival; the comparison of T0–T1 explored the effect of immunotherapy. Results: A total of 22 patients were accrued: 64% current heavy smokers, 36% female and 14% had PS = 2. At T0, ROC analysis showed that IL-6, IL-8, IL-10 and TGF-β were higher in patients with poor survival. Cox analysis demonstrated that only patients with the IL-6 and TGF-β discriminate had good or poor survival, respectively. Longitudinal increments of CCL-4, IL-15, IL-2 and CXCL-10 were observed in all patients during nivolumab treatment. Conclusion: In this small population with poor clinical characteristics, this study highlights the prognostic role of IL-6 and TGF-β. Nivolumab treatment is associated with a positive modulation of some Th1 cytokines, but it does not correlate with the outcome.

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“…Our group has used PCA to identify a cytokinome signature able to discriminate different prognostic groups among end-stage patients affected by different solid tumors [ 44 ] and in breast cancer patients to identify a signature potentially able to select patients for treatment beyond progression [ 45 ]. However, to the best of our knowledge, this is the first study on colorectal cancer using PCA to evaluate a cytokine profile in patients with metastatic disease treated with standard therapy.…”

Section: Discussionmentioning

confidence: 99%

Baseline Cytokine Profile Identifies a Favorable Outcome in a Subgroup of Colorectal Cancer Patients Treated with Regorafenib

Abbona

Ricci²,

Paccagnella

et al. 2023

Vaccines

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Metastatic colorectal cancer is frequently associated with poor clinical conditions that may limit therapeutic options. Regorafenib is a small molecule approved for the treatment of metastatic colorectal cancer, but it is hampered by significative toxicities. Moreover, only a relatively limited number of patients benefit from the treatment. Therefore, the identification of reliable markers for response is an unmet need. Eighteen cytokines, selected based on their prevalent Th1 or Th2 effects, were collected. Peripheral blood samples were gathered at baseline in 25 metastatic colorectal cancer patients treated with regorafenib. Data extracted have been linked to progression-free survival. ROC identified the best cytokines associated with outcome. The relative value of the selected cytokines was determined by PCA. Data analysis identified 8 cytokines (TGF-β, TNF-α, CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21), used to create a signature (TGF-β, TNF-α high; CCL-2, IL-6, IL-8, IL-10, IL-13 and IL-21 low) corresponding to patients with a significantly longer progression-free survival. This report suggests that the analysis of multiple cytokines might identify a cytokine signature related to a patient’s outcome that is able to recognize patients who will benefit from treatment. If confirmed, future studies, also based on different drugs, using this approach and including larger patient populations, might identify a signature allowing the a priori identification of patients to be treated.

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Cytokine Profiling of End Stage Cancer Patients Treated with Immunotherapy

Cited by 3 publications

References 35 publications

Plasma Chemokine C-C Motif Ligand 2 as a Potential Biomarker for Prostate Cancer

Plasma Chemokine C-C Motif Ligand 2 as a Potential Biomarker for Prostate Cancer

Baseline Values of Circulating IL-6 and TGF-β Might Identify Patients with HNSCC Who Do Not Benefit from Nivolumab Treatment

Baseline Cytokine Profile Identifies a Favorable Outcome in a Subgroup of Colorectal Cancer Patients Treated with Regorafenib

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