Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(6), С. e009063 - e009063

Опубликована: Июнь 1, 2024

Cancer immunotherapy has flourished over the last 10–15 years, transforming practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, bispecific T engagers, a vaccine, an oncolytic virus have joined cytokines as standard cancer care. At same scientific progress delivered vast amounts new knowledge. For example, advances in technologies such single-cell sequencing spatial transcriptomics provided deep insights into immunobiology tumor microenvironment. With rapid progress, field is currently at critical inflection point, with potential exponential growth next decade. Recognizing this, Society Immunotherapy convened diverse group experts representing academia, pharmaceutical biotechnology industries, patient advocacy, regulatory community identify current opportunities challenges goal prioritizing areas highest impact. The consensus identified seven high-priority opportunity field: mechanisms antitumor activity toxicity; drug resistance; biomarkers biospecimens; unique aspects novel therapeutics; host environmental interactions; premalignant immunity, interception, immunoprevention; trial design, endpoints, conduct. Additionally, roadblocks were discussed, several topics cross-cutting tools optimization, each impact multiple priority areas. These include preclinical models, data curation sharing, biopsies biospecimens, diversification funding sources, definitions standards, engagement. Finally, key guiding principles that will both optimize maximize field. engaging community; cultivating diversity, equity, inclusion, accessibility; leveraging power artificial intelligence accelerate progress. Here, we present outcomes these discussions strategic vision galvanize decade immunotherapy.

Язык: Английский

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Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers

Cancers, Год журнала: 2022, Номер 14(4), С. 1028 - 1028

Опубликована: Фев. 17, 2022

Though early-stage colorectal cancer has a high 5 year survival rate of 65–92% depending on the specific stage, this probability drops to 13% after metastasizes. Frontline treatments for such as chemotherapy and radiation often produce dose-limiting toxicities in patients acquired resistance cells. Additional targeted are needed improve patient outcomes quality life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules engage train immune system kill Preclinical clinical investigations immunotherapy including checkpoint blockade, adoptive cell therapy, monoclonal oncolytic anti-cancer vaccines, modulators have been promising, but demonstrate limitations proficient mismatch repair enzymes. In review, we discuss preclinical studies investigating predictive biomarkers response these treatments. We also consider open questions optimal combination maximize efficacy, minimize toxicity, prevent approaches sensitize repair-proficient immunotherapy.

Язык: Английский

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Immune Checkpoint Inhibitors—Associated Cardiotoxicity

Cancers, Год журнала: 2022, Номер 14(5), С. 1145 - 1145

Опубликована: Фев. 23, 2022

Large population-based studies examining differences in ICI-associated cardiotoxicity across cancer types and agents are limited. Data of 5518 patients who received at least one cycle ICIs were extracted from a large network health care organizations. ICI treatment groups classified by the first agent(s) (ipilimumab, nivolumab, pembrolizumab, cemiplimab, avelumab, atezolizumab, or durvalumab) its class (PD-1 inhibitors, PD-L1 CTLA4-inhibitors, their combination (ipilimumab + nivolumab)). Time to cardiac adverse event (CAE) (arrhythmia, acute myocardial infarction, myocarditis, cardiomyopathy, pericarditis) developed within year after initiation was analyzed using competing-risks regression model adjusting for groups, patient demographic clinical characteristics, sites. By month 12, 12.5% cardiotoxicity. The most common arrhythmia (9.3%) 2.1% myocarditis. After characteristics sites, initiated on monotherapy with ipilimumab (adjusted Hazard Ratio (aHR): 2.00; 95% CI: 1.49−2.70; p < 0.001) pembrolizumab (aHR: 1.21; 1.01−1.46; = 0.040) had higher risk developing CAEs compared nivolumab monotherapy. Ipilimumab use may increase other agents. Avelumab also estimated highly elevated 1.92; 0.85−4.34; 0.117) agents, although estimate did not reach statistical significance, warranting future studies.

Язык: Английский

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Identification of molecular subtypes and a novel prognostic model of diffuse large B-cell lymphoma based on a metabolism-associated gene signature

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Апрель 25, 2022

Diffuse large B cell lymphoma (DLBCL) is the most common in adults. Metabolic reprogramming tumors closely related to immune microenvironment. This study aimed explore interactions between metabolism-associated genes (MAGs) and DLBCL prognosis their potential associations with microenvironment.Gene expression clinical data on patients were obtained from GEO database. Metabolism-associated molecular subtypes identified by consensus clustering. A prognostic risk model containing 14 MAGs was established using Lasso-Cox regression training cohort. It then validated internal testing cohort TCGA external validation GO, KEGG GSVA used differences enriched pathways high- low-risk groups. ESTIMATE, CIBERSORT, ssGSEA analyses assess Finally, WGCNA analysis identify two hub among MAGs, they preliminarily verified our tissue microarray (TMA) multiple fluorescence immunohistochemistry (mIHC).Consensus clustering divided into metabolic significant Poor associated an immunosuppressive constructed based it classify groups; high-risk group had poorer microenvironment characterized low score, status, high abundance of cells, checkpoints. Cox regression, ROC curve analysis, a nomogram indicated that independent factor better value than International Prognostic Index (IPI) score. The underwent validations verification TMA consistent results bioinformatics analyses.The proposed are both promising classifications DLBCL, which may provide novel insights for developing accurate targeted cancer therapies.

Язык: Английский

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The role of mitochondria in the resistance of melanoma to PD-1 inhibitors

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Май 23, 2023

Abstract Malignant melanoma is one of the most common tumours and has highest mortality rate all types skin cancers worldwide. Traditional novel therapeutic approaches, including surgery, targeted therapy immunotherapy, have shown good efficacy in treatment melanoma. At present, mainstay for immunotherapy combined with other strategies. However, immune checkpoint inhibitors, such as PD-1 are not particularly effective clinical patients Changes mitochondrial function may affect development inhibitors. To elucidate role mitochondria resistance to this review comprehensively summarises occurrence melanoma, targets related cells changes different resistant This help develop strategies improving response inhibitors prolonging survival by activating tumour T cells.

Язык: Английский

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Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine

Cancers, Год журнала: 2022, Номер 14(9), С. 2241 - 2241

Опубликована: Апрель 29, 2022

Immune Checkpoint Inhibitors (ICIs) are well recognized as a major immune treatment modality for multiple types of solid cancers. However, colorectal cancer (CRC), ICIs only approved the Mismatch-Repair-Deficient and Microsatellite Instability-High (dMMR/MSI-H) tumors. For vast majority CRC, that not dMMR/MSI-H, alone provide limited to no clinical benefit. This discrepancy response between CRC other cancers suggests may be inherently resistant alone. In translational research, efforts underway thoroughly characterize microenvironment better understand mechanisms behind this resistance find new biomarkers response. clinic, trials being set up study along with treatments targeting newly discovered checkpoint molecules or combining existing therapies improve in MSS CRC. review, we will focus on characteristics discuss promising studied recent therapies.

Язык: Английский

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How Did Conventional Nanoparticle-Mediated Photothermal Therapy Become “Hot” in Combination with Cancer Immunotherapy?

Cancers, Год журнала: 2022, Номер 14(8), С. 2044 - 2044

Опубликована: Апрель 18, 2022

One of the promising cancer treatment methods is photothermal therapy (PTT), which has achieved good therapeutic efficiency through nanoparticle-based photoabsorbers. Because various functions nanoparticles, such as targeting properties, high light-to-heat conversion, and photostability, nanoparticle-mediated PTT successfully induces damage in tumor tissues with minimal side effects on surrounding healthy tissues. The efficacy originates from cell membrane disruption, protein denaturation, DNA by light-induced heat, but these biological impacts only influence localized areas. This conventional still attracts attention a novel immunotherapy, because causes immune responses against cancer. PTT-induced immunogenic death activates cells for systemic anti-cancer effect. Additionally, excellent compatibility other (e.g., chemotherapy checkpoint blockade therapy) reinforces combined immunotherapy. In this review, we investigate agents nanoparticles compare their applications to reveal how undergoes transition thermotherapy

Язык: Английский

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Pancreatic Ductal Adenocarcinoma and Immune Checkpoint Inhibitors: The Gray Curtain of Immunotherapy and Spikes of Lights

Current Oncology, Год журнала: 2023, Номер 30(4), С. 3871 - 3885

Опубликована: Март 30, 2023

Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with poor 5-year overall survival rate (~10%). The revolution of immunotherapy in clinical oncology has not substantially changed outcome for patients PDAC. Despite outstanding efforts, neither immune checkpoint inhibitors (ICIs) alone, nor combination chemotherapy or targeted therapies have shown encouraging results. This failure mirrors the lack knowledge about real key players system senescence and complexity tumor microenvironment However, some hope can be derived from PARP-inhibitor combinations, vaccines, CAR-T-cells therapy. In this review, we comprehensively summarize latest updates use ICIs PDAC, focusing on evidence ongoing studies highlighting explanations possible solutions.

Язык: Английский

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The Immune Landscape of Breast Cancer: Strategies for Overcoming Immunotherapy Resistance

Cancers, Год журнала: 2021, Номер 13(23), С. 6012 - 6012

Опубликована: Ноя. 29, 2021

Breast cancer (BC) has traditionally been considered to be not inherently immunogenic and insufficiently represented by immune cell infiltrates. Therefore, for a long time, it was thought that the immunotherapies targeting this type of its microenvironment were justified would bring benefits breast patients. Nevertheless, date, considerable number reports have indicated tumor-infiltrating lymphocytes (TILs) as prognostic clinically relevant biomarker in cancer. A high TILs expression demonstrated primary tumors, both, HER2-positive BC triple-negative (TNBC), patients before treatment, well after treatment with adjuvant neoadjuvant chemotherapy. Another milestone reached advanced TNBC immunotherapy help checkpoint inhibitors directed against PD-L1 molecule. Although those findings, together recent developments chimeric antigen receptor T therapies, show immense promise significant advancements treatments, there are still various obstacles optimal activity immunotherapeutics treatment. Of these, immunosuppressive tumor constitutes key barrier greatly hinders success most aggressive types cancer, TNBC. improvement current demand development new immunotherapeutic strategies is strongly warranted.

Язык: Английский

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New Therapeutic Strategies for Adult Acute Myeloid Leukemia

Cancers, Год журнала: 2022, Номер 14(11), С. 2806 - 2806

Опубликована: Июнь 5, 2022

Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy. Chromosomal and genetic analyses are important for the diagnosis prognosis of AML. Some patients experience relapse or have refractory disease, despite conventional cytotoxic chemotherapies allogeneic transplantation, variety new agents treatment strategies emerged. After over 20 years during which no drugs became available AML, CD33-targeting antibody-drug conjugate gemtuzumab ozogamicin was developed. This currently used in combination with standard chemotherapy as single agent. CPX-351, liposomal formulation containing daunorubicin cytarabine, has become one treatments secondary AML elderly. FMS-like tyrosine kinase 3 (

Язык: Английский

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