Journal of Immunotherapy最新文献

{"title":"Dimethyl Fumarate Mediates Glutathione Metabolism to Drive Cuproptosis and Activate the Antitumor Function of CD8+ T Cells Against Liver Cancer.","authors":"Jianqiao Kong, Jianjun Tang, Peng Zhang, Yun Zhao, Yang Dai, Zhenghua Ding","doi":"10.1097/CJI.0000000000000620","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000620","url":null,"abstract":"<p><p>Dimethyl fumarate (DMF) exerts cytoprotective effects via antioxidant pathway activation. Whether it modulates antitumor immunity through novel cell death forms remains unclear. GSH/GSSG levels were measured in HCC and adjacent tissues using assay kits, with FDX1 and GCLM expression detected by IHC. Cuproptosis-related proteins (NRF2, FDX1, LIAS) and DLAT oligomerization were assessed by western blotting and immunofluorescence in HCC cells. Intracellular GSH, glutamate, Cu2+, and γ-GCS activity were measured biochemically. Cell viability was determined by CCK-8. CD8+ T cells cocultured with HCC cells were analyzed for GZMB, IFN-γ, and TNF-α by flow cytometry; cytotoxicity was evaluated by LDH release. HCC tissues exhibited elevated GSH, downregulated FDX1, and upregulated GCLM compared with adjacent tissues. Elesclomol-Cu2+ (ES-Cu) induced cuproptosis, upregulating NRF2, downregulating FDX1 and LIAS, promoting DLAT oligomerization, and causing GSH depletion and Cu2+ accumulation; GSH-MEE reversed these effects. DMF inhibited GSH metabolism, evidenced by NRF2 downregulation, decreased GSH, increased GSSG, and suppressed γ-GCS activity. Mechanistically, DMF promoted cuproptosis via NRF2 inhibition, which was reversed by NRF2 overexpression. DMF-induced cuproptosis enhanced TNF-α, IFN-γ, and GZMB expression and increased CD8+ T-cell cytotoxicity; the copper chelator tetrathiomolybdate blocked these effects. DMF induces cuproptosis by modulating GSH metabolism, thereby activating CD8+ T-cell-mediated anti-HCC immunity. This offers potential targets for novel combination therapeutic strategies.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features, Treatment, and Outcomes of Sintilimab-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.","authors":"Zhaoquan Wu, Yong Pan, Miao Liu, Wei Sun, Chunjiang Wang","doi":"10.1097/CJI.0000000000000622","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000622","url":null,"abstract":"<p><p>To explore the clinical characteristics of sintilimab-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and provide references for prevention, diagnosis, and treatment. Clinical reports of sintilimab-induced SJS/TEN published before March 31st, 2026 were collected by searching the database, and clinical data were extracted for retrospective analysis. Twenty-three men (69.7%) and ten women (30.3%) were included, with a median age of 66 years (range: 27, 82). The median time for the appearance of SJS/TEN was 20 days (range: 2, 240), and the median cycle was 1 cycle (range: 1, 17). Among these 33 patients, 72.7% were diagnosed with TEN, 15.2% with SJS, and 12.1% with SJS/TEN overlap. The main clinical symptoms were rash (75.0%), erosion (82.1%), bullae/blisters (78.6%), erythema (67.9%), epidermal detachment (57.1%), and pruritus (50.0%), high fever (46.4%), and ocular symptoms (35.7%). Furthermore, 57.6% of the patients experienced mucosal lesions, mainly affecting the mouth (89.5%), genitalia (57.9%), and conjunctiva (52.6%). Skin biopsy showed poptotic keratinocytes (83.3%), subepidermal blisters (50.0%), and inflammatory cell infiltration (100%). After discontinuing sintilimab and receiving systemic steroids and intravenous immunoglobulins (IVIG) treatment, 87.9% of the patients experienced improvement in skin symptoms, while 12.1% of the patients died from TEN. SJS/TEN is a rare and life-threatening cutaneous adverse reaction of sintilimab. During the use of sintilimab, clinicians should be aware of the possibility of SJS/TEN, especially within the first month. For patients diagnosed with SJS/TEN, sintilimab should be discontinued, and they should receive systemic steroids and IVIG treatment.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Side Effect Management of Immune-related Hepatotoxicity Due to Immune Checkpoint Inhibitors: A Multicenter Study by the Turkish Oncology Group (TOG).","authors":"Ozden Demir, Bulent Cetin, Ali Alkan, Nilay Sengul, Canberk Sencan, Ilknur Deliktas Onur, Muzaffer Ugraklı, Sinem Akbas, Eda Ercin, Elif Sahin, Abdussamet Celebi, Zehra Sucuoglu Isleyen, Teoman Sakalar, Saadet Sim, Sevinc Ballı, Canan Karan, Alper Topal, Abdullah Sakin, Yesim Agyol, Goncagul Akdag, Melek Ozdemir, Leman Tomak, Saadettin Kılıckap","doi":"10.1097/CJI.0000000000000604","DOIUrl":"10.1097/CJI.0000000000000604","url":null,"abstract":"<p><p>The mechanism by which immune checkpoint inhibitors (ICI) cause immune-mediated liver injury is unclear. In 2017, the Society for Immunotherapy of Cancer (SITC) published guidelines for managing immunotherapy toxicity. This article aims to compile clinical approaches to cases of hepatotoxicity associated with immunotherapies (ILICI) in a multicenter setting. This will contribute to the literature by providing data from a larger number of patients. This article is important for ILICI clinical management because it enables the continuation of treatment and raises awareness of these immunotherapy side effects. The study included 56 patients from 20 centers. Grade 3-4 hepatic insufficiency occurred in 24 patients (42.9%). Five (8.9%) patients died due to hepatic insufficiency. Liver biopsies of these 5 patients were consistent with ILICI. The median number of treatment cycles before ILICI developed was 5 (minimum: one, maximum: 80). Steroid therapy was administered to all patients except 6. Eighteen patients who were unresponsive to steroids received various second-line treatments. Some patients received various treatments, such as third-, fourth-, and fifth-line treatments, after the second-line treatment. There was no significant correlation between the median number of ICI cycles and serious adverse events (AST, ALT, bilirubin, and hepatic failure) ( P =0.186, P =1.000, P =0.599, and P =0.484). In addition, no significant correlation was observed between grade 3-4 adverse events and ICI treatment in the first versus subsequent lines ( P >0.05). ILICI is a rare but serious condition, so the treatment modalities used are important. We believe raising awareness of ILICI and evaluating second-line treatments used in steroid-refractory cases contributes to the literature by pooling these treatments together.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"284-289"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Armoring CAR-T Cells Against Exhaustion: Engineering Strategies for Glioblastoma.","authors":"Ali Anvarian, Fatemeh S M Nazari, Ali Karimi Jashni","doi":"10.1097/CJI.0000000000000617","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000617","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most lethal primary brain tumor, with a median survival of 15 months despite intensive treatment. Chimeric antigen receptor (CAR) T-cell therapy, while transformative in hematological malignancies, consistently fails in GBM because the immunosuppressive tumor microenvironment (TME) drives T-cell exhaustion. We examined transcriptional programs, microenvironmental factors, and metabolic competition that collectively drive exhaustion in this context. Then we reviewed 5 convergent engineering strategies: localized cytokine delivery to bypass autocrine deficits; adjunctive antibody therapies to remodel the TME; oncolytic viruses armed with chemoattractants or cytokines as immunomodulators; coexpression of cytokine or chemokine receptors to provide survival signals; and multiplexed CRISPR-Cas9 editing to disrupt exhaustion checkpoints and enable site-specific CAR integration. Locoregional delivery consistently outperforms systemic administration, demonstrating that physical barriers are as critical as cellular engineering. Despite this progress, antigen heterogeneity, metabolic limitations, and the need for combinatorial targeting remain the principal unresolved challenges. An overview of the key concepts discussed in this review is presented in the graphical abstract.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Culture and Expansion of Tumor-Infiltrating Lymphocyte From Biopsy Tissue Samples of Gastric Cancer Are Feasible.","authors":"Bitna Park, Hanna Park, Min-Jung Seo, Sung W Kim, In-Pyo Baek, Young W Kim, Hark K Kim","doi":"10.1097/CJI.0000000000000607","DOIUrl":"10.1097/CJI.0000000000000607","url":null,"abstract":"<p><p>Adoptive transfer of tumor-infiltrating lymphocytes (TILs) achieves promising clinical results in solid tumors. TIL trials use surgically resected tissue to isolate TILs. However, certain tissues are difficult to surgically resect, and a minimally invasive approach might be advantageous if it could achieve similar TIL yields. We tested a minimally invasive approach to culture and expand TILs using endoscopic biopsy tumors from patients with metastatic gastric cancer (GC). TILs were successfully cultured from all of the intestinal GC biopsies, while TIL populations had slow growth from diffuse GCs. Initial TIL growth was faster in intestinal GC biopsies (n=9) than in diffuse GC biopsies (n=4) ( P =0.021). All 4 biopsy TILs tested were expanded >10 10 by our rapid expansion protocol. Biopsy TILs demonstrated equivalent expansion and FACS profiles to TILs cultured from gastrectomy. Thus, clinical-grade TILs can be successfully cultured and expanded from endoscopic biopsy tumors in patients with metastatic GC.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"240-244"},"PeriodicalIF":2.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Translational Modification Mediated By Acylation Modification Related Genes Induces Immunosuppression and Immunotherapy Resistance in Head and Neck Squamous Cell Carcinoma.","authors":"Youwei Li, Xinqing Liu, Jinzhi Wu","doi":"10.1097/CJI.0000000000000594","DOIUrl":"10.1097/CJI.0000000000000594","url":null,"abstract":"<p><p>Acylation modification plays a crucial role in modulating head and neck squamous cell carcinoma (HNSCC) progression, and their specific prognostic implications in HNSCC have not been thoroughly investigated. Eleven acylation modifications (AM) (crotonylation, lactylation, succinylation, benzoylation, butyrylation, malonylation, glutarylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, palmitoylation, myristoylation, and prenylation) were generated consensus cluster. Then, WGCNA was utilized to identify module genes. Finally, a machine learning approach was used to create AM.score. This analysis revealed 2 distinct subtypes of AMs, each characterized by unique molecular signatures. By integrating different categories of genes, including DEGs, module genes, and AM-related genes, 16 hub genes were identified, and an AM.score was developed. AM.score was rigorously validated across independent external cohorts (TCGA-HNSCC, GSE41613, GSE42743, and GSE65858) and an in-house cohort, demonstrating its reliability and potential applicability. The AM.score serves a dual purpose in its application, as it encapsulates the essential clinical context and offers valuable insights regarding the efficacy of immunotherapy treatments. In particular, patients categorized with a high AM.score displayed a TME that was more actively engaged, which corresponded with a poor prognosis. Furthermore, these patients demonstrated a high level of responsiveness to immunotherapy interventions. Furthermore, an examination using scRNA-seq indicated that patients with high AM.score exhibited heightened cell proliferation and malignancy. This novel AM.score could effectively assess the prognosis and therapeutic responses of HNSCC patients, providing new perspectives for individualized treatment for the patient population.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"225-239"},"PeriodicalIF":2.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-Related Adverse Events Among Patients With Endometrial Cancer Receiving Pembrolizumab Alone or With Other Treatments: A Single-Center Real-World Experience.","authors":"Glenn Boyles, Chelsey Vranes, Nikita Sinha, Emily Broaddus, Victoria Bae-Jump, Benjamin Albright, Olivia Lara","doi":"10.1097/CJI.0000000000000603","DOIUrl":"10.1097/CJI.0000000000000603","url":null,"abstract":"<p><p>Immunotherapy has revolutionized endometrial cancer (EC) treatment; our objectives were to characterize immune-related adverse events (irAE) among EC patients and to identify factors associated with risk for irAE. Patients who received pembrolizumab alone or as part of combination therapy for advanced/recurrent EC from 2014 to 2025 were identified. Baseline demographics and cancer characteristics were collected. Potential immune-related adverse events were collected and graded for the cohort. Multiple logistic regression was then performed. A total of 180 patients were included. The mean age was 63.9 years. Black patients comprised 30.6% of the cohort. Endometrioid was the commonest histologic subtype (38.7%), and most tumors (67.7%) were MMR proficient. Ninety-five patients (52.8%) had any-grade irAE, and 14 (7.8%) experienced serious (grades 3-4) irAE. Hypothyroidism was the most common irAE overall (n = 37; 20.6%,) followed by fatigue (n = 23; 12.8%) and diarrhea (n = 20; 11.1%). The most common serious irAEs were diarrhea (n = 4; 2.2%,) followed by hepatitis, dermatitis, and pneumonitis (each n = 3; 1.7%). On univariate analysis, older age, uninsured status, and receipt of pembrolizumab with lenvatinib were associated with any-grade irAE (all P <0.05). In our multiple logistic regression model, uninsured status was an independent predictor of both any-grade irAE (aOR: 5.49; 95% CI: 1.03-29.2) and serious irAE (aOR: 7.96; 95% CI: 1.44-43.9). Receiving pembrolizumab with lenvatinib was independently associated with any-grade irAE (aOR: 7.13; 95% CI: 2.92-17.4). Uninsured status and coadministration with lenvatinib may increase the risk for pembrolizumab-associated irAE among patients with EC. Further collection of real-world data, including unexplored social and economic factors and novel biomarkers, may predict irAE and ultimately help guide clinical decision-making.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"245-251"},"PeriodicalIF":2.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13252962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Communication: Personalized Circulating Tumor DNA as a Predictor of Pathologic Response in Neoadjuvant Treatment of Resectable Melanoma.","authors":"Justine V Cohen, Mofei Liu, Grace Rogers, Michael Manos, Patricia McHugh, Ashley Schwer, Patrick A Ott, Ann W Silk, Karam Khaddour, Elizabeth I Buchbinder, William J Gibson, Frank Stephen Hodi, Hillary C Tsibris","doi":"10.1097/CJI.0000000000000605","DOIUrl":"10.1097/CJI.0000000000000605","url":null,"abstract":"<p><p>Patients with resectable stage III-IV melanoma are at high risk of recurrence following surgical excision. Neoadjuvant therapy (NEO) with immune checkpoint inhibition (ICI) improves event-free survival and may allow for pathologic treatment response assessment with potential adjuvant therapy de-escalation. Identification of a biomarker correlated with tumor response could facilitate individualized therapeutic decision-making. This study investigates the utility of circulating tumor DNA (ctDNA) as a predictive biomarker of pathologic response in melanoma treated with NEO ICI. We identified melanoma patients treated with NEO ICI at Dana-Farber Cancer Institute and measured personalized ctDNA plasma levels pretreatment, before each NEO ICI cycle, and postoperatively. We evaluated whether ctDNA levels during the NEO course correlated with graded pathologic response. Of 18 patients who underwent NEO ICI, there were 10 pathologic complete responses (pCR; 0% viable tumor), 1 pathologic near-complete response (near pCR; >0% but ≤10% viable tumor), 1 partial response (pPR; >10%-≤50% viable tumor), and 6 nonresponses (pNR; >50% viable tumor). Responders (pCR, near pCR, or pPR) were more likely to have negative presurgical ctDNA levels (100% (12/12) vs. 33% (2/6), P =0.005). In addition to absolute levels, ctDNA kinetics during NEO ICI were also predictive of pathologic response, with nonresponders more likely to show an increase in ctDNA levels between the first and final ICI cycles compared with responders (mean change ctDNA (SD), 0.09 (0.15) vs. -1.16 (3.31), P =0.004). These findings underscore the potential of ctDNA as a dynamic biomarker to inform response-driven, personalized treatment strategies following NEO ICI.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"252-255"},"PeriodicalIF":2.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features, Treatment, and Outcomes of Sintilimab-Induced Myocarditis.","authors":"Miao Liu, Wei Sun, Yong Pan, Chunjiang Wang","doi":"10.1097/CJI.0000000000000589","DOIUrl":"10.1097/CJI.0000000000000589","url":null,"abstract":"<p><p>To examine the clinical characteristics of sintilimab-induced myocarditis and to provide evidence for its diagnosis and management. Retrospective analysis was conducted on clinical case reports of sintilimab-induced myocarditis documented before July 31, 2025. A total of 34 patients were included, with a median age of 64 years (range: 33-85), including 23 (67.6%) male cases. The onset of myocarditis ranged from 1 to 120 days post-treatment, with a median onset of 21 days. The primary clinical presentations included dyspnea (41.2%), chest tightness (35.3%), palpitations (17.6%), and shortness of breath (14.7%), with some cases remaining asymptomatic (8.8%). Comorbid immune-related adverse events included myasthenia gravis (44.1%), myositis (17.6%), and hepatitis (17.6%). Laboratory findings often revealed elevated cardiac troponin I, N-terminal probrain natriuretic peptide, creatine kinase MB, and lactate dehydrogenase. The electrocardiogram mainly showed atrioventricular block (41.2%), ST-T segment changes (44.1%), and atrial or ventricular arrhythmias (50.0%). Echocardiography examination can show normal (34.5%), left ventricular diastolic dysfunction (31.0%), left atrial enlargement (13.8%), and pericardial effusion (13.8%). Cardiac magnetic resonance imaging may show normal (42.9%), myocardial edema (28.6%), and delayed myocardial enhancement (28.6%). Coronary angiography showed normal (73.3%) and coronary artery stenosis of the lumen (26.7%). All patients discontinued sintilimab and received steroid and intravenous immunoglobulin treatment. Outcomes indicated that 79.4% recovered from myocarditis, while 20.6% succumbed. Sintilimab-induced myocarditis has nonspecific manifestations and a high mortality rate. Myasthenia gravis and myositis can occur simultaneously with myocarditis. During simtimab treatment, it is necessary to closely monitor cardiac parameters and symptoms.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"49 5","pages":"209-213"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulsed Electrical Field Ablation Plus Intratumoral Immunotherapy for Hepatocellular Carcinoma.","authors":"Erik Soule, Carlos Vargas, Ramon Sanchez, Eduardo Cortes, Nathan Goodyear, Renata Barco, Jason Williams","doi":"10.1097/CJI.0000000000000596","DOIUrl":"10.1097/CJI.0000000000000596","url":null,"abstract":"<p><p>The fourth leading cause of cancer death worldwide, hepatocellular carcinoma, is known to progress relentlessly and recur despite treatment. Given the high tumor mutational burden, hepatocellular carcinoma is an attractive target for immunotherapy. Early trials of systemic checkpoint inhibitors have produced promising results, although complete and durable immunologic tumor eradication remains elusive. Pulsed electrical field ablation is a nonthermal ablation technology that causes apoptosis of diseased cells, while preserving the neoantigens for subsequent immune recognition by antigen-presenting cells and effectors. The neoantigens are released when the membrane is permeabilized. Furthermore, pulsed electrical field ablation was shown to induce the formation of tertiary lymphoid structures, congregations of immune cells that form inside the tumor at the ablation site, analogous to a lymph node. We present a novel treatment regimen with pulsed electrical field ablation combined with intratumoral immunotherapy injection. Treatments were performed using computed tomography guidance in a percutaneous manner. Pulsed electrical field ablation was performed within the tumor using the Aliya pulsed electrical field system (Galvanize, Redwood City, CA). After ablation was performed, the immunotherapy was administered into the tumor, mixed with iodinated contrast for visibility and gelfoam slurry for local retention. Three patients underwent treatment, and all treated tumors responded favorably with a decrease in size and a marked decrease in postcontrast enhancement. There were no treatment-related complications or high-grade toxicities. Pulsed electrical field ablation plus intratumoral immunotherapy may be safe and effective for the treatment of advanced hepatocellular carcinoma.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"49 5","pages":"214-224"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}