Eosinophils and melanoma: Implications for immunotherapy

Robinson, India; Lucia, Gabriella Santa; Li, Andraia R.; Oberholtzer, Nathaniel; Plante, John; Quinn, Kristen M.; Reuben, Daniel Y.; Mehrotra, Shikhar; Valdebran, Manuel

doi:10.1111/pcmr.13025

Cited by 10 publications

(8 citation statements)

References 104 publications

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“…Even though NLR and dNLR may appear similar at a glance, the dNLR may be more informative than NLR, because it includes monocytes as well as other granulocyte subpopulations, such as eosinophils. Recent observational investigations indicated that eosinophil counts and serum levels of the eosinophil cationic protein are significantly associated with prolonged survival in metastatic CM [32]. Finally, we acknowledge that our study presents two major limitations: (1) it is a retrospective study without a validation or control cohort and (2) the sample size included in this study was comprised of a small number of CM patients, possibly resulting in statistically insignificant results which could have likely been avoided using a larger study population.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Performance of the Derived Neutrophil-to-Lymphocyte Ratio in Stage IV Melanoma Patients Treated with Immune Checkpoint Inhibitors

Gambichler

Mansour

Scheel

et al. 2022

Dermato

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The purpose was to evaluate the prognostic performance of the derived neutrophil–to-lymphocyte ratio (dNLR) in patients with metastatic cutaneous melanoma (CM) treated with immune checkpoint inhibitors (ICI). We retrospectively investigated 41 CM patients with stage IV disease who had the indication for treatment with ICI. dNLR as well as NLR were routinely determined prior to the start of ICI treatment. The dNLR and NLR were calculated as follows: dNLR = absolute neutrophil counts (ANC)/white blood cell count −ANC and NRL = ANC/absolute lymphocyte counts, respectively. Follow-up of the patients was performed in line with current guidelines. In univariate analysis, dNLR (p = 0.027 and p = 0.032) as well as NLR (p = 0.0023 and p = 0.0036) were the only parameters which were significantly associated with the best overall response (BOR) and disease control rate (DCR) on ROC curve analyses. NLR negatively correlated with CM-specific survival (r = −0.32, p = 0.043). CM-specific deaths were significantly associated with the absence of immune-related adverse events (p = 0.043), elevated S100 calcium-binding protein B (S100B) at baseline (p = 0.0006), and dNLR (p = 0.024). In multivariate analyses, NLR was the only significant independent predictor for BOR (p = 0.014; odds ratio: 1.7; and 95% CI 1.11 to 2.61) and DCR (p = 0.019; odds ratio: 1.5; and 95% CI 1.07 to 2.19). Regarding CM-specific death, however, normal baseline S100B was the only significant independent predictor (p = 0.0020; odds ratio: 0.074; and 95% CI 0.014 to 0.38) for survival. Our data demonstrate that baseline NLR seems to be superior to dNLR in the prediction of ICI response in CM patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic Performance of the Derived Neutrophil-to-Lymphocyte Ratio in Stage IV Melanoma Patients Treated with Immune Checkpoint Inhibitors

Gambichler

Mansour

Scheel

et al. 2022

Dermato

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“…This is consistent with our experiment where we observed an association between MAIT cell-mediated inhibition of MC38-derived tumors and an increase in tumor production of GM-CSF and eotaxin-1 production in the tumors. With eosinophils’ known ability to release effector molecules like major basic protein (MBP) into the tumor microenvironment to induce cancer cell lysis (55), these data support the involvement of eosinophils in MAIT-mediated tumor suppression.…”

Section: Discussionmentioning

confidence: 89%

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth

Cheng,

Lebish,

Jensen

et al. 2024

Preprint

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Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions. Despite their potential for adoptive cell therapy, studies into their anti-cancer activity, including their role in colon cancer, are limited. We expanded MAIT cells in vivo and injected them into RAG1-/- mice with MC38-derived tumors and tumor growth was assessed. Peritumoral injection of MAIT cells inhibits tumor growth compared to control. Genomic and multiplex cytokine analyses show that tumors from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting an association between eosinophil recruitment and tumor inhibition. Multiplex cytokine and flow cytometry analyses of human peripheral leukocytes stimulated with MAIT ligand show an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. We documented that MAIT cells have a protective role in a murine colon cancer model, potentially involving novel eosinophil-associated mechanisms. This study provides evidence of the immune modulating potential of MAIT cells within the tumor microenvironment, leading to compositional and functional changes. Our results highlight the potential of MAIT cells for colon cancer immunotherapy.

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“…There were also significant differences among studies concerning the association between eosinophilic granulocyte count and treatment response. Despite the extremely heterogeneous data, eosinophils could serve as a prognostic marker in immunotherapy of melanoma, given their effects on the TME and the relationship between TME and ICI-therapy response ( 27 , 57 ). In a retrospective cohort based on a pharmacovigilance registry that included 909 patients with various tumors receiving anti-PD-1 or anti-PD-L1 therapy, 2.8% of patients were found to have immune-related eosinophilia, the majority of whom were being treated for advanced melanoma ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Eosinophilic granulocytes as a potential prognostic marker for cancer progression and therapeutic response in malignant melanoma

Brand,

Hunger,

Seyed Jafari

2024

Front. Oncol.

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The importance of eosinophilic granulocytes in cancer has been widely discussed in recent years. The current study reviews the evidence on the role of eosinophilic granulocytes in melanoma as a prognostic marker for cancer progression and the efficacy of treatment with modern immune checkpoint inhibitors. A total of 33 human clinical studies were included in the review, with heterogeneous data due to differences in patients populations, study design and inclusion of small study groups. However, 28 of the 33 studies suggested that eosinophilic granulocytes could be used as a prognostic biomarker for outcome and/or potential response to systemic treatment and/or occurrence of adverse events in melanoma patients. Nevertheless, the exact role of eosinophils remains to be elucidated. Further prospective, larger and better controlled studies are warranted to clarify the significance of eosinophilic granulocytes in patients with melanoma, in more details.

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Eosinophils and melanoma: Implications for immunotherapy

Cited by 10 publications

References 104 publications

Prognostic Performance of the Derived Neutrophil-to-Lymphocyte Ratio in Stage IV Melanoma Patients Treated with Immune Checkpoint Inhibitors

Prognostic Performance of the Derived Neutrophil-to-Lymphocyte Ratio in Stage IV Melanoma Patients Treated with Immune Checkpoint Inhibitors

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth

Eosinophilic granulocytes as a potential prognostic marker for cancer progression and therapeutic response in malignant melanoma

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