Oncoimmunology最新文献

{"title":"CD39⁺ conventional CD4⁺ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade.","authors":"Sabrina N Bossio, Carolina Abrate, Jimena Tosello Boari, Constanza Rodriguez, Fernando P Canale, María C Ramello, Valentina Brunotto, Wilfrid Richer, Dario Rocha, Christine Sedlik, Anne Vincent-Salomon, Edith Borcoman, Andres Del Castillo, Adriana Gruppi, Elmer Fernandez, Eva V Acosta Rodríguez, Eliane Piaggio, Carolina L Montes","doi":"10.1080/2162402X.2023.2246319","DOIUrl":"10.1080/2162402X.2023.2246319","url":null,"abstract":"<p><p>Conventional CD4⁺ T (Tconv) lymphocytes play important roles in tumor immunity; however, their contribution to tumor elimination remains poorly understood. Here, we describe a subset of tumor-infiltrating Tconv cells characterized by the expression of CD39. In several mouse cancer models, we observed that CD39⁺ Tconv cells accumulated in tumors but were absent in lymphoid organs. Compared to tumor CD39^- counterparts, CD39⁺ Tconv cells exhibited a cytotoxic and exhausted signature at the transcriptomic level, confirmed by high protein expression of inhibitory receptors and transcription factors related to the exhaustion. Additionally, CD39⁺ Tconv cells showed increased production of IFN<math><mi>γ</mi></math>, granzyme B, perforin and CD107a expression, but reduced production of TNF. Around 55% of OVA-specific Tconv from B16-OVA tumor-bearing mice, expressed CD39. <i>In vivo</i> CTLA-4 blockade induced the expansion of tumor CD39⁺ Tconv cells, which maintained their cytotoxic and exhausted features. In breast cancer patients, CD39⁺ Tconv cells were found in tumors and in metastatic lymph nodes but were less frequent in adjacent non-tumoral mammary tissue and not detected in non-metastatic lymph nodes and blood. Human tumor CD39⁺ Tconv cells constituted a heterogeneous cell population with features of exhaustion, high expression of inhibitory receptors and CD107a. We found that high CD4 and ENTPD1 (CD39) gene expression in human tumor tissues correlated with a higher overall survival rate in breast cancer patients. Our results identify CD39 as a biomarker of Tconv cells, with characteristics of both exhaustion and cytotoxic potential, and indicate CD39⁺ Tconv cells as players within the immune response against tumors.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44017676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNBC-derived Gal3BP/Gal3 complex induces immunosuppression through CD45 receptor.","authors":"Annat Raiter,&nbsp;Julia Lipovetsky,&nbsp;Asaf Stenbac,&nbsp;Ido Lubin,&nbsp;Rinat Yerushalmi","doi":"10.1080/2162402X.2023.2246322","DOIUrl":"10.1080/2162402X.2023.2246322","url":null,"abstract":"<p><p>A preliminary study investigating immunotherapy strategies for aggressive triple negative breast cancer (TNBC) revealed an overexpression of genes involved in the release of extracellular vesicles (EVs). Proteins expressed by EVs play a role in reprogramming the tumor microenvironment and impeding effective responses to immunotherapy. Galectin 3 (Gal3), found in the extracellular space of breast cancer cells, downregulates T-cell receptor expression. Gal3 binds to several receptors, including CD45, which is required for T-cell receptor activation. Previously, we reported a novel tumor escape mechanism, whereby TNBC cells suppress immune cells through CD45 intracellular signals. The objective of this study was to determine the potential association of Gal3 with TNBC-secreted EVs induction of immunosuppression via the CD45 signaling pathway. EVs were isolated from MDA-MB-231 cells and the plasma of patients with TNBC. Mass spectrometry revealed the presence of Gal3 binding protein (Gal3BP) in the isolated small EVs, which interacted with TNBC secreted Gal3. Gal3BP and Gal3 form a complex that induces a significant increase in T-regulatory cells in peripheral blood mononuclear cells (PBMCs). This increase correlates with a significant increase in suppressive interleukins 10 and 35. Blocking the CD45 receptor in PBMCs cultured with tumor-derived EVs impeded the immunosuppression exerted by the Gal3BP/Gal3 complex. This led to an increase in IFN-γ and the activation of CD4, CD8 and CD56 effector cells. This study suggests a tumor escape mechanism that may contribute to the development of a different immunotherapy strategy that complements current therapies used for TNBC.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/98/KONI_12_2246322.PMC10431740.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanoma patients with immune-related adverse events after immune checkpoint inhibitors are characterized by a distinct immunological phenotype of circulating T cells and M-MDSCs.","authors":"Alisa Lepper,&nbsp;Rebekka Bitsch,&nbsp;Feyza Gül Özbay Kurt,&nbsp;Ihor Arkhypov,&nbsp;Samantha Lasser,&nbsp;Jochen Utikal,&nbsp;Viktor Umansky","doi":"10.1080/2162402X.2023.2247303","DOIUrl":"10.1080/2162402X.2023.2247303","url":null,"abstract":"<p><p>Treatment with immune checkpoint inhibitors (ICIs) has improved the prognosis of melanoma patients. However, ICIs can cause an overactivation of the immune system followed by diverse immunological side effects known as immune-related adverse events (irAE). Currently, the toxicity of irAE is limiting the usage of ICIs. Here, we studied circulating monocytic myeloid-derived suppressor cells (M-MDSCs) and T cells in course of irAE after the ICI therapy. Our longitudinal study involved 31 melanoma patients with and without adverse events during anti-PD-1 monotherapy or anti-CTLA-4/PD-1 combination therapy. Peripheral blood samples were analyzed before ICI start, during ICI treatment, at the time point of irAE and during immunosuppressive treatment to cure irAE. We observed an enhanced progression-free survival among patients with irAE. In patients with irAE, we found an upregulation of CD69 on CD8⁺ T cells and a decreased frequency of regulatory T cells (Tregs). Moreover, lower frequencies of Tregs correlated with more severe side effects. Patients treated with immunomodulatory drugs after irAE manifestation tend to show an elevated number of M-MDSCs during an immunosuppressive therapy. We suggest that an activation of CD8⁺ T cells and the reduction of Treg frequencies could be responsible for the development of irAE.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/05/KONI_12_2247303.PMC10431726.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The yes-associated protein (YAP) is associated with resistance to anti-GD2 immunotherapy in neuroblastoma through downregulation of <i>ST8SIA1</i>.","authors":"Adeiye A Pilgrim, Hunter C Jonus, Andrew Ho, Anna C Cole, Jenny Shim, Kelly C Goldsmith","doi":"10.1080/2162402X.2023.2240678","DOIUrl":"10.1080/2162402X.2023.2240678","url":null,"abstract":"<p><p>Pediatric patients with high-risk neuroblastoma often relapse with chemotherapy-resistant, incurable disease. Relapsed neuroblastomas harbor chemo-resistant mesenchymal tumor cells and increased expression/activity of the transcriptional co-regulator, the Yes-Associated Protein (YAP). Patients with relapsed neuroblastoma are often treated with immunotherapy such as the anti-GD2 antibody, dinutuximab, in combination with chemotherapy. We have previously shown that YAP mediates both chemotherapy and MEK inhibitor resistance in relapsed <i>RAS</i> mutated neuroblastoma and so posited that YAP might also be involved in anti-GD2 antibody resistance. We now show that YAP genetic inhibition significantly enhances sensitivity of mesenchymal neuroblastomas to dinutuximab and gamma delta (γδ) T cells both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, YAP inhibition induces increased GD2 cell surface expression through upregulation of <i>ST8SIA1</i>, the gene encoding GD3 synthase and the rate-limiting enzyme in GD2 biosynthesis. The mechanism of <i>ST8SIA1</i> suppression by YAP is independent of <i>PRRX1</i> expression, a mesenchymal master transcription factor, suggesting YAP may be the downstream effector of mesenchymal GD2 resistance. These results therefore identify YAP as a therapeutic target to augment GD2 immunotherapy responses in patients with neuroblastoma.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/ae/KONI_12_2240678.PMC10405770.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10197735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD11c⁺ and IRF8⁺ cell densities in rectal cancer biopsies predict outcomes of neoadjuvant chemoradiotherapy.","authors":"Benita C Y Tse, Sarah Bergamin, Pascal Steffen, George Hruby, Nick Pavlakis, Stephen J Clarke, Justin Evans, Alexander Engel, Andrew Kneebone, Mark P Molloy","doi":"10.1080/2162402X.2023.2238506","DOIUrl":"10.1080/2162402X.2023.2238506","url":null,"abstract":"<p><p>Approximately 20% of locally advanced rectal cancer (LARC) patients treated preoperatively with chemoradiotherapy (CRT) achieve pathologically confirmed complete regression. However, there are no clinically implemented biomarkers measurable in biopsies that are predictive of tumor regression. Here, we conducted multiplexed immunophenotyping of rectal cancer diagnostic biopsies from 16 LARC patients treated preoperatively with CRT. We identified that patients with greater tumor regression had higher tumor infiltration of pan-T cells and IRF8⁺HLA-DR⁺ cells prior to CRT. High IRF8⁺HLA-DR⁺ cell density was further associated with prolonged disease-specific survival with 83% survival at 5 y compared to 28% in patients with low infiltration. Contrastingly, low CD11c⁺ myeloid cell infiltration prior to CRT was a putative biomarker associated with longer 3- and 5-y disease-free survival. The results demonstrate the potential use of rectal cancer diagnostic biopsies to measure IRF8⁺ HLA-DR⁺ cells as predictors of CRT-induced tumor regression and CD11c⁺ myeloid cells as predictors of LARC patient survival.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/5b/KONI_12_2238506.PMC10361136.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10564738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updates on radiotherapy-immunotherapy combinations: Proceedings of 6^th annual ImmunoRad conference.","authors":"Fabiana Gregucci, Sheila Spada, Mary Helen Barcellos-Hoff, Nina Bhardwaj, Charleen Chan Wah Hak, Alba Fiorentino, Chandan Guha, Monica L Guzman, Kevin Harrington, Fernanda G Herrera, Jamie Honeychurch, Theodore Hong, Lorea Iturri, Elisabeth Jaffee, Sana D Karam, Simon R V Knott, Constantinos Koumenis, David Lyden, Ariel E Marciscano, Alan Melcher, Michele Mondini, Anna Mondino, Zachary S Morris, Sean Pitroda, Sergio A Quezada, Laura Santambrogio, Stephen Shiao, John Stagg, Irma Telarovic, Robert Timmerman, Marie-Catherine Vozenin, Ralph Weichselbaum, James Welsh, Anna Wilkins, Chris Xu, Roberta Zappasodi, Weiping Zou, Alexandre Bobard, Sandra Demaria, Lorenzo Galluzzi, Eric Deutsch, Silvia C Formenti","doi":"10.1080/2162402X.2023.2222560","DOIUrl":"10.1080/2162402X.2023.2222560","url":null,"abstract":"<p><p>Focal radiation therapy (RT) has attracted considerable attention as a combinatorial partner for immunotherapy (IT), largely reflecting a well-defined, predictable safety profile and at least some potential for immunostimulation. However, only a few RT-IT combinations have been tested successfully in patients with cancer, highlighting the urgent need for an improved understanding of the interaction between RT and IT in both preclinical and clinical scenarios. Every year since 2016, ImmunoRad gathers experts working at the interface between RT and IT to provide a forum for education and discussion, with the ultimate goal of fostering progress in the field at both preclinical and clinical levels. Here, we summarize the key concepts and findings presented at the Sixth Annual ImmunoRad conference.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/fc/KONI_12_2222560.PMC10286673.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trial watch: an update of clinical advances in photodynamic therapy and its immunoadjuvant properties for cancer treatment.","authors":"Mafalda Penetra, Luís G Arnaut, Lígia C Gomes-da-Silva","doi":"10.1080/2162402X.2023.2226535","DOIUrl":"10.1080/2162402X.2023.2226535","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) is a medical treatment used to target solid tumors, where the administration of a photosensitizing agent and light generate reactive oxygen species (ROS), thus resulting in strong oxidative stress that selectively damages the illuminated tissues. Several preclinical studies have demonstrated that PDT can prime the immune system to recognize and attack cancer cells throughout the body. However, there is still limited evidence of PDT-mediated anti-tumor immunity in clinical settings. In the last decade, several clinical trials on PDT for cancer treatment have been initiated, indicating that significant efforts are being made to improve current PDT protocols. However, most of these studies disregarded the immunological dimension of PDT. The immunomodulatory properties of PDT can be combined with standard therapy and/or emerging immunotherapies, such as immune checkpoint blockers (ICBs), to achieve better disease control. Combining PDT with immunotherapy has shown synergistic effects in some preclinical models. However, the value of this combination in patients is still unknown, as the first clinical trials evaluating the combination of PDT with ICBs are just being initiated. Overall, this Trial Watch provides a summary of recent clinical information on the immunomodulatory properties of PDT and ongoing clinical trials using PDT to treat cancer patients. It also discusses the future perspectives of PDT for oncological indications.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10563995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming the immunosuppressive tumor microenvironment results in successful clearance of tumors resistant to radiation therapy and anti-PD-1/PD-L1.","authors":"Debayan Mukherjee, Erminia Romano, Richard Walshaw, Leo A H Zeef, Antonia Banyard, Stephen J Kitcatt, Eleanor J Cheadle, Karoliina Tuomela, Swati Pendharkar, Aws Al-Deka, Beatrice Salerno, Sophie Raby, Ian G Mills, Jamie Honeychurch, Tim M Illidge","doi":"10.1080/2162402X.2023.2223094","DOIUrl":"10.1080/2162402X.2023.2223094","url":null,"abstract":"<p><p>Despite breakthroughs in immune checkpoint inhibitors (ICI), the majority of tumors, including those poorly infiltrated by CD8+ T cells or heavily infiltrated by immunosuppressive immune effector cells, are unlikely to result in clinically meaningful tumor responses. Radiation therapy (RT) has been combined with ICI to potentially overcome this resistance and improve response rates but reported clinical trial results have thus far been disappointing. Novel approaches are required to overcome this resistance and reprogram the immunosuppressive tumor microenvironment (TME) and address this major unmet clinical need. Using diverse preclinical tumor models of prostate and bladder cancer, including an autochthonous prostate tumor (Pten^-/-/trp53^-/-) that respond poorly to radiation therapy (RT) and anti-PD-L1 combinations, the key drivers of this resistance within the TME were profiled and used to develop rationalized combination therapies that simultaneously enhance activation of anti-cancer T cell responses and reprogram the immunosuppressive TME. The addition of anti-CD40mAb to RT resulted in an increase in IFN-y signaling, activation of Th-1 pathways with an increased infiltration of CD8+ T-cells and regulatory T-cells with associated activation of the CTLA-4 signaling pathway in the TME. Anti-CTLA-4mAb in combination with RT further reprogrammed the immunosuppressive TME, resulting in durable, long-term tumor control. Our data provide novel insights into the underlying mechanisms of the immunosuppressive TME that result in resistance to RT and anti-PD-1 inhibitors and inform therapeutic approaches to reprogramming the immune contexture in the TME to potentially improve tumor responses and clinical outcomes.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA analysis of Natural Killer cell-derived exosomes: the microRNA let-7b-5p is enriched in exosomes and participates in their anti-tumor effects against pancreatic cancer cells.","authors":"Anna Laura Di Pace, Andrea Pelosi, Piera Filomena Fiore, Nicola Tumino, Francesca Besi, Linda Quatrini, Silvia Santopolo, Paola Vacca, Lorenzo Moretta","doi":"10.1080/2162402X.2023.2221081","DOIUrl":"10.1080/2162402X.2023.2221081","url":null,"abstract":"<p><p>Natural Killer (NK) cells are important components of the immune system in the defense against tumor growth and metastasis. They release exosomes containing proteins and nucleic acids, including microRNAs (miRNAs). NK-derived exosomes play a role in the anti-tumor NK cell function since they are able to recognize and kill cancer cells. However, the involvement of exosomal miRNAs in the function of NK exosomes is poorly understood. In this study, we explored the miRNA content of NK exosomes by microarray as compared to their cellular counterparts. The expression of selected miRNAs and lytic potential of NK exosomes against childhood B acute lymphoblastic leukemia cells after co-cultures with pancreatic cancer cells were also evaluated. We identified a small subset of miRNAs, including miR-16-5p, miR-342-3p, miR-24-3p, miR-92a-3p and let-7b-5p that is highly expressed in NK exosomes. Moreover, we provide evidence that NK exosomes efficiently increase let-7b-5p expression in pancreatic cancer cells and induce inhibition of cell proliferation by targeting the cell cycle regulator CDK6. Let-7b-5p transfer by NK exosomes could represent a novel mechanism by which NK cells counteract tumor growth. However, both cytolytic activity and miRNA content of NK exosomes were reduced upon co-culture with pancreatic cancer cells. Alteration in the miRNA cargo of NK exosomes, together with their reduced cytotoxic activity, could represent another strategy exerted by cancer to evade the immune response. Our study provides new information on the molecular mechanisms used by NK exosomes to exert anti-tumor-activity and offers new clues to integrate cancer treatments with NK exosomes.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/23/KONI_12_2221081.PMC10251800.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trial watch: immunotherapeutic strategies on the horizon for hepatocellular carcinoma.","authors":"Benjamin Koh, Darren Jun Hao Tan, Wen Hui Lim, Jeffrey S L Wong, Cheng Han Ng, Kai En Chan, Meng Wang, Wei Peng Yong, Yock Young Dan, Louis Z Wang, Nigel Tan, Mark Muthiah, Alfred Kow, Nicholas L Syn, Daniel Q Huang, Thomas Yau","doi":"10.1080/2162402X.2023.2214478","DOIUrl":"10.1080/2162402X.2023.2214478","url":null,"abstract":"<p><p>The use of immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 and CTLA-4 has transformed the oncology practice of hepatocellular carcinoma. However, only 25-30% of the patients with advanced HCC treated with atezolizumab-bevacizumab or tremelimumab-durvalumab (STRIDE) respond initially, and mechanistic biomarkers and novel treatment strategies are urgently needed for patients who present with or acquire resistance to first-line ICI-based therapies. The recent approval of the STRIDE regimen has also engendered new questions, such as patient selection factors (e.g. portal hypertension and history of variceal bleed) and biomarkers, and the optimal combination and sequencing of ICI-based regimens. Triumphs in the setting of advanced HCC have also galvanized considerable interest in the broader application of ICIs to early- and intermediate-stage diseases, including clinical combination of ICIs with locoregional therapies. Among these clinical contexts, the role of ICIs in liver transplantation - which is a potentially curative strategy unique to HCC management - as a bridge to liver transplant in potential candidates or in the setting of post-transplant recurrence, warrants investigation in view of the notable theoretical risk of allograft rejection. In this review, we summarize and chart the landscape of seminal immuno-oncology trials in HCC and envision future clinical developments.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/1b/KONI_12_2214478.PMC10241000.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10191411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}