Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Predictive factors of neoadjuvant immune checkpoint blockade in melanoma.

ABSTRACT: This review describes the current body of literature and ongoing clinical trials examining neoadjuvant immune checkpoint inhibitors (ICI) for patients with resectable stage III and IV melanoma. Based on prior success in treating metastatic melanoma and as adjuvant therapy, ICIs are being explored in the neoadjuvant setting. There have been initial trials and there are many ongoing trials examining neoadjuvant ICI. Herein, we will review the clinical feasibility and efficacy of various neoadjuvant ICI regimens, explore pathologic and cellular responses, and present factors associated with predictive tumor response.

SUBMITTER: Sarver M

PROVIDER: S-EPMC9122309 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Predictive factors of neoadjuvant immune checkpoint blockade in melanoma.

Sarver Melissa M Brown Michael C MC Rhodin Kristen E KE Salama April K S AKS Beasley Georgia M GM

Human vaccines & immunotherapeutics 20210713 3

This review describes the current body of literature and ongoing clinical trials examining neoadjuvant immune checkpoint inhibitors (ICI) for patients with resectable stage III and IV melanoma. Based on prior success in treating metastatic melanoma and as adjuvant therapy, ICIs are being explored in the neoadjuvant setting. There have been initial trials and there are many ongoing trials examining neoadjuvant ICI. Herein, we will review the clinical feasibility and efficacy of various neoadjuvan ...[more]

PMID: 34254900

Similar Datasets

Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.

Project description:Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment1; however, optimal regimens have not been defined. Here we report results from a randomized phase 2 study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma ( NCT02519322 ). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs) and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. These results describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers.

| S-EPMC6481682 | biostudies-literature

Factors Determining Long-Term Antitumor Responses to Immune Checkpoint Blockade Therapy in Melanoma.

Project description:With the increasing promise of long-term survival with immune checkpoint blockade (ICB) therapies, particularly for patients with advanced melanoma, clinicians and investigators are driven to identify prognostic and predictive factors that may help to identify individuals who are likely to experience durable benefit. Several ICB combinations are being actively developed to expand the armamentarium of treatments for patients who may not achieve long-term responses to ICB single therapies alone. Thus, negative predictive markers are also of great interest. This review seeks to deepen our understanding of the mechanisms underlying the durability of ICB treatments. We will discuss the currently available long-term data from the ICB clinical trials and real-world studies describing the survivorship of ICB-treated melanoma patients. Additionally, we explore the current treatment outcomes in patients rechallenged with ICB and the patterns of ICB resistance based on sites of disease, namely, liver or CNS metastases. Lastly, we discuss the landscape in melanoma in the context of prognostic or predictive factors as markers of long-term response to ICB.

| S-EPMC8787112 | biostudies-literature

The Role of Immune Checkpoint Blockade in Uveal Melanoma.

Project description:Uveal melanoma (UM) represents the most common intraocular malignancy in adults and accounts for about 5% of all melanomas. Primary disease can be effectively controlled by several local therapy options, but UM has a high potential for metastatic spread, especially to the liver. Despite its clinical and genetic heterogeneity, therapy of metastatic UM has largely been adopted from cutaneous melanoma (CM) with discouraging results until now. The introduction of antibodies targeting CTLA-4 and PD-1 for immune checkpoint blockade (ICB) has revolutionized the field of cancer therapy and has achieved pioneering results in metastatic CM. Thus, expectations were high that patients with metastatic UM would also benefit from these new therapy options. This review provides a comprehensive and up-to-date overview on the role of ICB in UM. We give a summary of UM biology, its clinical features, and how it differs from CM. The results of several studies that have been investigating ICB in metastatic UM are presented. We discuss possible reasons for the lack of efficacy of ICB in UM compared to CM, highlight the pitfalls of ICB in this cancer entity, and explain why other immune-modulating therapies could still be an option for future UM therapies.

| S-EPMC7037664 | biostudies-literature

Progress and Challenges of Predictive Biomarkers for Immune Checkpoint Blockade.

Project description:Over the past decade, immune checkpoint blockade (ICB) therapy has revolutionized the outlook for oncology with significant and sustained improvement in the overall patient survival. Unlike traditional cancer therapies, which target the cancer cells directly, ICB acts on the immune system to enhance anti-tumoral immunity. However, the response rate is still far from satisfactory and most patients are refractory to such treatment. Unfortunately, the mechanisms underlying such heterogeneous responses between patients to ICB therapy remain unclear. In addition, escalating costs of cancer care and unnecessary immune-related adverse events also are pertinent considerations with applications of ICB. Given these issues, identifying explicit predictive biomarkers for patient selection is an urgent unmet need to increase the efficacy of ICB therapy. The markers can be classified as tumor related and non-tumor-related biomarkers. Although substantial efforts have been put into investigating various biomarkers, none of them has been found to be sufficient for effectively stratifying patients who may benefit from immunotherapy. The present write up is an attempt to review the various emerging clinically relevant biomarkers affecting the efficacy of immune checkpoint inhibitors, as well as the limitations associated with their clinical application.

| S-EPMC7992906 | biostudies-literature

Neoadjuvant immune checkpoint inhibitors in high-risk stage III melanoma.

Project description:The success of immunotherapy and targeted therapy for metastatic melanoma has generated considerable interest in the adjuvant setting, even though high-risk stage III melanoma (with or without in-transit metastases) still holds a substantial probability of relapse, despite surgical resection and available adjuvant treatments. Based on preclinical and clinical trials in resectable melanoma, immune checkpoint inhibitors can enhance anti-tumor immunity by activating antigen-specific T cells found in the primary site. These tumor-reactive T cells continue to exert their anti-tumor effects on remaining neoplastic cells after resection of the primary tumor, potentially preventing relapses from reoccurring. Several trials in the neoadjuvant setting have been conducted for melanoma patients using checkpoint inhibitors with promising early data, showing an improvement of operability and clinical outcomes. Hence, in this study, we review and discuss the available published and ongoing clinical trials to explore the scientific background behind immunotherapy in the neoadjuvant context.

| S-EPMC9122306 | biostudies-literature

Predictors of responses to immune checkpoint blockade in advanced melanoma.

Project description:Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab?+?nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.

| S-EPMC5605517 | biostudies-literature

Molecular patterns of resistance to immune checkpoint blockade in melanoma.

Project description:Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collect biopsies from a cohort of 44 patients with melanoma after progression on anti-CTLA4 or anti-PD1 monotherapy. Genetic alterations of antigen presentation and interferon gamma signaling pathways are observed in approximately 25% of ICB resistant cases. Anti-CTLA4 resistant lesions have a sustained immune response, including immune-regulatory features, as suggested by multiplex spatial and T cell receptor (TCR) clonality analyses. One anti-PD1 resistant lesion harbors a distinct immune cell niche, however, anti-PD1 resistant tumors are generally immune poor with non-expanded TCR clones. Such immune poor microenvironments are associated with melanoma cells having a de-differentiated phenotype lacking expression of MHC-I molecules. In addition, anti-PD1 resistant tumors have reduced fractions of PD1+ CD8+ T cells as compared to ICB naïve metastases. Collectively, these data show the complexity of ICB resistance and highlight differences between anti-CTLA4 and anti-PD1 resistance that may underlie differential clinical outcomes of therapy sequence and combination.

| S-EPMC11004175 | biostudies-literature

Tumor-infiltrating lymphocytes as a predictive biomarker of cutaneous immune-related adverse events after immune checkpoint blockade in patients with advanced melanoma.

Project description: Not available

| S-EPMC10796159 | biostudies-literature

Neoadjuvant Immune Checkpoint Inhibitor Therapy in Melanoma: Efficacy, Safety and Timing.

Project description:The introduction of effective systemic therapies has significantly changed the treatment of stage III and IV melanoma. Both immune checkpoint inhibitors and targeted therapies have improved recurrence-free survival in the adjuvant setting. Recent interest has sparked for neoadjuvant systemic therapy with immune checkpoint inhibitors. The intended benefit of pre-operative treatment with immunotherapy is amongst others to enable tailoring of the surgery and adjuvant systemic therapy according to the treatment response. Most importantly, recurrence-free survival might be improved by neoadjuvant systemic therapy over the current standard of care of surgery followed by adjuvant systemic therapy. The first phase I and II trials investigating anti-PD1 inhibitors, both as a single agent and in combination with anti-CTLA-4 inhibitors or other therapeutic agents, have shown promising results. Pathological complete response on neoadjuvant systemic therapy seems a valid surrogate endpoint for relapse-free and overall survival. Pathological complete response rates in these trials vary between 30 and 70%. The optimal dose with respect to efficacy and toxicity and the interval between systemic and surgical treatment remain important issues to address. Accumulating follow-up data and ongoing phase III studies must prove if neoadjuvant systemic therapy is superior to surgery followed by standard-of-care adjuvant therapy.

| S-EPMC9148869 | biostudies-literature

Neoadjuvant checkpoint blockade for cancer immunotherapy.

Project description:Cancer immunotherapies that target the programmed cell death 1 (PD-1):programmed death-ligand 1 (PD-L1) immune checkpoint pathway have ushered in the modern oncology era. Drugs that block PD-1 or PD-L1 facilitate endogenous antitumor immunity and, because of their broad activity spectrum, have been regarded as a common denominator for cancer therapy. Nevertheless, many advanced tumors demonstrate de novo or acquired treatment resistance, and ongoing research efforts are focused on improving patient outcomes. Using anti-PD-1 or anti-PD-L1 treatment against earlier stages of cancer is hypothesized to be one such solution. This Review focuses on the development of neoadjuvant (presurgical) immunotherapy in the era of PD-1 pathway blockade, highlighting particular considerations for biological mechanisms, clinical trial design, and pathologic response assessments. Findings from neoadjuvant immunotherapy studies may reveal pathways, mechanisms, and molecules that can be cotargeted in new treatment combinations to increase anti-PD-1 and anti-PD-L1 efficacy.

| S-EPMC7789854 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data