Personalizing neoadjuvant immune-checkpoint inhibition in patients with melanoma

Lucas, Minke W.; Versluis, Judith M.; Rozeman, Elisa A.; Blank, Christian U.

doi:10.1038/s41571-023-00760-3

Cited by 25 publications

(10 citation statements)

References 127 publications

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“…The greatest potential risk of the neoadjuvant strategy is that in the case of non-responders, progression of the disease during neoadjuvant treatment can prevent planned curative-intent surgical treatment of localized disease, if the disease becomes unresectable or spreads to distant sites [ 13 ]. Therefore, if neoadjuvant treatment is considered, it is especially important to anticipate the response of patients to the treatment and expected disease-free survival and provide them with personalized and optimized therapy—this can be achieved using predictive and prognostic biomarkers [ 13 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…In general, predictive biomarkers are supposed to predict whether the patient will respond to the specific treatment considered, while prognostic biomarkers allow for the anticipation of survival or the time to disease recurrence [ 26 ]. It is expected that when selecting a treatment modality with the highest chance of response in the case of each individual patient—determined by appropriate biomarkers—a higher efficacy of the treatment will be observed [ 22 ]. Other potential roles of biomarkers, measured during the course of neoadjuvant treatment, are to support the decision, whether the administration of adjuvant therapy is appropriate or to support the selection of the most effective subsequent therapy, in the case of a recurrent disease [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is expected that when selecting a treatment modality with the highest chance of response in the case of each individual patient—determined by appropriate biomarkers—a higher efficacy of the treatment will be observed [ 22 ]. Other potential roles of biomarkers, measured during the course of neoadjuvant treatment, are to support the decision, whether the administration of adjuvant therapy is appropriate or to support the selection of the most effective subsequent therapy, in the case of a recurrent disease [ 22 ]. Furthermore, prognostic biomarkers are expected to determine the risk of recurrence of the disease and therefore allow the optimization of the follow-up schedule [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Molecular and Clinicopathological Biomarkers in the Neoadjuvant Treatment of Patients with Advanced Resectable Melanoma

Błoński,

Czarnecka,

Ostaszewski

et al. 2024

Biomedicines

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Neoadjuvant systemic therapy is emerging as the best medical practice in patients with resectable stage III melanoma. As different regimens are expected to become available in this approach, the improved optimization of treatment strategies is required. Personalization of care in each individual patient—by precisely determining the disease-related risk and the most efficient therapeutic approach—is expected to minimize disease recurrence, but also the incidence of treatment-related adverse events and the extent of surgical intervention. This can be achieved through validation and clinical application of predictive and prognostic biomarkers. For immune checkpoint inhibitors, there are no validated predictive biomarkers until now. Promising predictive molecular biomarkers for neoadjuvant immunotherapy are tumor mutational burden and the interferon-gamma pathway expression signature. Pathological response to neoadjuvant treatment is a biomarker of a favorable prognosis and surrogate endpoint for recurrence-free survival in clinical trials. Despite the reliability of these biomarkers, risk stratification and response prediction in the neoadjuvant setting are still unsatisfactory and represent a critical knowledge gap, limiting the development of optimized personalized strategies in everyday practice.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular and Clinicopathological Biomarkers in the Neoadjuvant Treatment of Patients with Advanced Resectable Melanoma

Błoński,

Czarnecka,

Ostaszewski

et al. 2024

Biomedicines

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“…4 To date, immunotherapy using RNA molecules, immunostimulatory agents, and immune-checkpoint inhibitors has become an increasingly common type of antitumor treatment. [5][6][7] Membrane vesicles (MVs) are spherical, lipid-bilayer, and nanosized (20-400 nm) structures secreted by bacteria during their growth in vitro and in vivo. 8 MVs were first observed in Escherichia coli about 50 years ago, and the MVs of Gram-negative bacteria are mainly released from the outer membrane, namely, outer membrane vesicles (OMVs).…”

Section: Introductionmentioning

confidence: 99%

Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway

Li,

Wang,

Liu

et al. 2024

IJN

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Introduction Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated. Methods MVs of Staphylococcus aureu s USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2–MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor. Results The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 μg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2–MVs (R 2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10 −3 μg. Antares2–MVs can directly target tumor tissues in vivo, and 20 μg/mL Antares2–MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo. Conclusion S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment.

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“…Surgery is an indispensable option to treat solid tumors; however, tumor recurrence after surgical resection poses huge threats to human health and is regarded as one of the leading causes for cancer-related deaths. , Despite the continuing progress in novel surgical methods and other theranostic modalities, residual microtumors that can be neither removed thoroughly by surgery nor detected rapidly often induce tumor relapse. , Therefore, optimizing postsurgical treatment strategies plays a critical role in overcoming tumor recurrence. Among these treatment methods, immunotherapy has received increasing attention and stands ready to join conventional treatment modalities as adjuvant therapeutic modality with the aim to activate the body’s immune system to clear up tumor cells. − Nevertheless, the inevitable local inflammation after surgery recruits a number of abnormal immune cells, especially M2-like tumor-associated macrophage (TAM) that promotes immune escape and survival of the residual tumor cells, eventually causing tumor recurrence, metastasis, and further progression. , Thus, exploring feasible strategies to repolarize TAM phenotypes from pro-tumorigenic M2-like TAMs to antitumorigenic M1-like TAMs displays great significance in remodeling postoperative inflammatory tumor microenvironment (TME) …”

mentioning

confidence: 99%

Chemoimmunotherapeutic Nanogel for Pre- and Postsurgical Treatment of Malignant Melanoma by Reprogramming Tumor-Associated Macrophages

Tang,

Fu,

Liu

et al. 2024

Nano Lett.

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Surgery is the primary method to treat malignant melanoma; however, the residual microtumors that cannot be resected completely often trigger tumor recurrence, causing tumorrelated mortality following melanoma resection. Herein, we developed a feasible strategy based on the combinational chemoimmunotherapy by cross-linking carboxymethyl chitosan (CMCS)originated polymetformin (PolyMet CMCS ) with cystamine to prepare stimuli-responsive nanogel (PMNG) owing to the disulfide bond in cystamine that can be cleaved by the massive glutathione (GSH) in tumor sites. Then, chemotherapeutic agent doxorubicin (DOX) was loaded in PMNG, which was followed by a hyaluronic acid coating to improve the overall biocompatibility and targeting ability of the prepared nanogel (D@HPMNG). Notably, PMNG effectively reshaped the tumor immune microenvironment by reprogramming tumor-associated macrophage phenotypes and recruiting intratumoral CD8 + T cells owing to the inherited immunomodulatory capability of metformin. Consequently, D@HPMNG treatment remarkably suppressed melanoma growth and inhibited its recurrence after surgical resection, proposing a promising solution for overcoming lethal melanoma recurrence.

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Personalizing neoadjuvant immune-checkpoint inhibition in patients with melanoma

Cited by 25 publications

References 127 publications

Molecular and Clinicopathological Biomarkers in the Neoadjuvant Treatment of Patients with Advanced Resectable Melanoma

Molecular and Clinicopathological Biomarkers in the Neoadjuvant Treatment of Patients with Advanced Resectable Melanoma

Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway

Chemoimmunotherapeutic Nanogel for Pre- and Postsurgical Treatment of Malignant Melanoma by Reprogramming Tumor-Associated Macrophages

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