Cancer immunology research最新文献

{"title":"Preclinical development of T cells engineered to express a T cell antigen coupler (TAC) targeting Claudin 18.2-positive solid tumors.","authors":"Stacey X Xu, Ling Wang, Philbert Ip, Ritu R Randhawa, Tania Benatar, Suzanna L Prosser, Prabha Lal, Alima Naim Khan, Thanyashanthi Nitya-Nootan, Gargi Thakor, Heather MacGregor, Danielle Hayes, Andrea Vucicevic, Princy Mathew, Sadhak Sengupta, Christopher W Helsen, Andreas G Bader","doi":"10.1158/2326-6066.CIR-24-0138","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0138","url":null,"abstract":"<p><p>The T cell antigen coupler (TAC) is a chimeric receptor that facilitates tumor antigen-specific activation of T cells by co-opting the endogenous T cell receptor complex in the absence of tonic signaling. Previous data demonstrates that TAC affords T cells with the ability to induce durable and safe anti-tumor responses in preclinical models of hematological and solid tumors. Here, we describe the preclinical pharmacology and safety of an autologous Claudin 18.2 (CLDN18.2)-directed TAC T cell therapy, TAC01-CLDN18.2, in preparation for a Phase I/II clinical study in subjects with CLDN18.2-positive solid tumors. Following a screen of putative TAC constructs, the specificity, activity, and cytotoxicity of TAC T cells expressing the final CLDN18.2-TAC receptor were evaluated in vitro and in vivo using gastric, gastroesophageal, and pancreatic tumor models as well as human cells derived from normal tissues. CLDN18.2-specific activity and cytotoxicity of CLDN18.2-TAC T cells were observed in coculture with various 2D tumor cultures naturally expressing CLDN18.2 as well as tumor spheroids. These effects occurred in models with low antigen levels and was positively associated with increasing CLDN18.2 expression. CLDN18.2-TAC T cells effectively eradicated established tumor xenografts in mice in the absence of observed off-target or on-target/off-tumor effects, elicited durable efficacy in recursive killing and tumor rechallenge experiments, and remained unreactive in coculture with human cells representing vital organs. Thus, the data demonstrate that CLDN18.2-TAC T cells can induce a specific and long-lasting anti-tumor response in various CLDN18.2-positive solid tumor models without notable TAC-dependent toxicities, supporting the clinical development of TAC01-CLDN18.2.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL-1 and TNFα Inflammation.","authors":"Nam Woo Cho, Sophia M Guldberg, Barzin Y Nabet, Jie Zeng Yu, Eun Ji Kim, Kamir J Hiam-Galvez, Jacqueline L Yee, Rachel DeBarge, Iliana Tenvooren, Naa Asheley Ashitey, Filipa Lynce, Deborah A Dillon, Jennifer M Rosenbluth, Matthew H Spitzer","doi":"10.1158/2326-6066.CIR-24-0416","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0416","url":null,"abstract":"<p><p>Resistance to immune checkpoint inhibitors (ICIs) is common, even in tumors with T cell infiltration. We thus investigated consequences of ICI-induced T cell infiltration in the microenvironment of resistant tumors. T cells and neutrophil numbers increased in ICI-resistant tumors following treatment, in contrast to ICI-responsive tumors. Resistant tumors were distinguished by high expression of IL-1 Receptor 1 (IL1R1), enabling a synergistic response to IL-1 and TNFα to induce G-CSF, CXCL1, and CXCL2 via NF-κB signaling, supporting immunosuppressive neutrophil accumulation in tumor. Perturbation of this inflammatory resistance circuit sensitized tumors to ICIs. Paradoxically, T cells drove this resistance circuit via TNF both in vitro and in vivo. Evidence of this inflammatory resistance circuit and its impact also translated to human cancers. These data support a mechanism of ICI resistance, wherein treatment-induced T cell activity can drive resistance in tumors responsive to IL-1 and TNFα, with important therapeutic implications.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement factor H is an ICOS ligand modulating Tregs in the glioma microenvironment.","authors":"Karolina I Smolag, Jakub Olszowka, Rebecca Rosberg, Elinn Johansson, Elisabet Marinko, Karin Leandersson, David J O'Connell, Valeria Governa, Emre Can Tuysuz, Mattias Belting, Alexander Pietras, Myriam Martin, Anna M Blom","doi":"10.1158/2326-6066.CIR-23-1092","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-23-1092","url":null,"abstract":"<p><p>The survival rate of glioma patients has not significantly increased in recent years despite aggressive treatment and advances in immunotherapy. The limited response to treatments is partially attributed to the immunosuppressive tumor microenvironment, where regulatory T cells (Tregs) play a pivotal role in immunological tolerance. In this study, we investigated the impact of complement factor H (FH) on Tregs within the glioma microenvironment and found that FH is an ICOS ligand. The binding of FH to this immune checkpoint molecule promoted the survival and function of Tregs and induced the secretion of TGF-beta (TGF-β) and IL-10, while also suppressing T-cell proliferation. We further demonstrated that cancer cells in human and mouse gliomas directly produce FH. Database investigations revealed that upregulation of FH expression was associated with the presence of Tregs and correlated with worse prognosis for glioma patients. We confirmed the effect of FH on glioma development in a mouse model, where FH knockdown was associated with decrease in number of ICOS+ Tregs and demonstrated a tendency of prolonged survival (p=0.064). Since the accumulation of Tregs represents a promising prognostic and therapeutic target, evaluating FH expression should be considered when assessing the effectiveness of and resistance to immunotherapies against glioma.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Level of expression of MHCI-presented neoepitopes influences tumor rejection by neoantigen-specific CD8+ T cells.","authors":"Li Deng, Scott R Walsh, Andrew Nguyen, Jordon M Inkol, Michael J Westerveld, Lan Chen, Nader El-Sayes, Karen L Mossman, Samuel T Workenhe, Yonghong Wan","doi":"10.1158/2326-6066.CIR-23-0639","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-23-0639","url":null,"abstract":"<p><p>Neoantigen-targeted therapy holds an array of benefits for cancer immunotherapy, but the identification of peptide targets with tumor rejection capacity remains a limitation. To better define the criteria dictating tumor rejection potential, we examined the capacity of high-magnitude T cell responses induced towards several distinct neoantigen targets to regress MC38 tumors. Surprisingly, despite their demonstrated immunogenicity, vaccine-induced T-cell responses were unable to regress established MC38 tumors or prevent tumor engraftment in a prophylactic setting. However, T cells were functional with robust killing capacity towards neoantigen peptide-loaded cells. Furthermore, tumor cell killing was rescued in proportion to the expression level or saturation of target peptide-loaded MHCs on the cell surface. Overall, this study demonstrates a pivotal role for target protein expression levels in modulating the tumor rejection capacity of neoantigens. Thus, inclusion of this metric, in addition to immunogenicity analysis, may benefit antigen prediction techniques to ensure the full anti-tumor effect of cancer vaccines.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient EZH2 suppression by Tazemetostat during in vitro expansion maintains T-cell stemness and improves adoptive T-cell therapy.","authors":"Yingqin Hou, Jaroslav Zak, Yujie Shi, Isaraphorn Pratumchai, Brandon Dinner, Wenjian Wang, Ke Qin, Evan W Weber, John R Teijaro, Peng Wu","doi":"10.1158/2326-6066.CIR-24-0089","DOIUrl":"10.1158/2326-6066.CIR-24-0089","url":null,"abstract":"<p><p>The histone methyltransferase enhancer of zeste homolog 2 (EZH2) plays important roles in T-cell differentiation, proliferation and function. Previous studies have demonstrated that genetic deletion of EZH2 in CD8+ or total T cells impairs their antiviral and antitumor activity, cytokine production and ability to expand upon rechallenge. Contrary to the detrimental role of deleting T cell-intrinsic EZH2, here we have demonstrated that transient inhibition of EZH2 in T cells prior to the phenotypic onset of exhaustion with a clinically approved inhibitor, Tazemetostat, delayed their dysfunctional progression and preserved T-cell stemness and polyfunctionality but had no negative impact on cell proliferation. Tazemetostat induced T-cell epigenetic reprogramming and increased the expression of the self-renewal T-cell transcription factor TCF1 by reducing H3K27 methylation at its promoter preferentially in rapidly dividing T cells. In a murine melanoma model, T cells depleted of EZH2 induced poor tumor control, whereas adoptively transferred T cells pretreated with tazemetostat exhibited superior antitumor immunity, especially when used in combination with anti-PD-1 blockade. Collectively, these data highlight the potential of transient epigenetic reprogramming by EZH2 inhibition to enhance adoptive T-cell immunotherapy.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent MEK Inhibition with GITR Costimulation Rescues T-cell Function for Increased Efficacy with CTLA-4 Blockade in Solid Tumor Models.","authors":"Lauren Dong, Hyejin Choi, Sadna Budhu, Isabell Schulze, Svena Verma, Levi M Mangarin, Valeria Estrada Nevarro, Nezar Mehanna, Jonathan F Khan, Divya Venkatesh, Daniel Thach, Neal Rosen, Jedd D Wolchok, Taha Merghoub","doi":"10.1158/2326-6066.CIR-23-0729","DOIUrl":"10.1158/2326-6066.CIR-23-0729","url":null,"abstract":"<p><p>MEK inhibitors (MEKi) have shown limited success as a treatment for MAPK/ERK pathway-dependent cancers due to various resistance mechanisms tumor cells can employ. CH5126766 (CKI27) is an inhibitor that binds to MEK and prevents release of RAF, reducing the relief of negative feedback commonly observed with other MEKis. We observed that CKI27 increased MHC expression in tumor cells and improved T cell-mediated killing. Yet, CKI27 also decreased T-cell proliferation, activation, and cytolytic activity by inhibiting the MAPK/ERK pathway that is activated downstream of T-cell receptor signaling. Therefore, we aimed to balance the positive and negative immunomodulatory effects of MEKis for optimal combination with immunotherapy. Intermittent administration of CKI27 allowed T cells to partially recover and costimulation via GITR and OX-40 agonist antibodies completely alleviated inhibition of function. In Kras mutant lung and colon tumor mouse models, intermittent CKI27 and anti-GITR significantly decreased tumor growth and prolonged survival when further combined with CTLA-4 immune checkpoint blockade. Moreover, this triple combination increased CD8+ and CD4+ T-cell proliferation, activation, and effector/memory subsets in the tumor-draining lymph nodes and tumors and led to intratumoral regulatory T-cell destabilization. These data, collectively, will allow for more informed decisions when optimizing combination regimens by overcoming resistance, reducing toxicity, and generating long-term immune responses.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1392-1408"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical B Cells Promote Cancer Progression and Poor Response to Bacillus Calmette-Guérin in Non-Muscle Invasive Bladder Cancer.","authors":"Priyanka Yolmo, Sadaf Rahimi, Stephen Chenard, Gwenaëlle Conseil, Danielle Jenkins, Kartik Sachdeva, Isaac Emon, Jake Hamilton, Minqi Xu, Manu Rangachari, Eva Michaud, Jose J Mansure, Wassim Kassouf, David M Berman, David R Siemens, Madhuri Koti","doi":"10.1158/2326-6066.CIR-23-1114","DOIUrl":"10.1158/2326-6066.CIR-23-1114","url":null,"abstract":"<p><p>Poor response to Bacillus Calmette-Guérin (BCG) immunotherapy remains a major barrier in the management of patients with non-muscle invasive bladder cancer (NMIBC). Multiple factors are associated with poor outcomes, including biological aging and female sex. More recently, it has emerged that a B-cell-infiltrated pretreatment immune microenvironment of NMIBC tumors can influence the response to intravesically administered BCG. The mechanisms underlying the roles of B cells in NMIBC are poorly understood. Here, we show that B-cell-dominant tertiary lymphoid structures (TLSs), a hallmark feature of the chronic mucosal immune response, are abundant and located close to the epithelial compartment in pretreatment tumors from BCG non-responders. Digital spatial proteomic profiling of whole tumor sections from male and female patients with NMIBC who underwent treatment with intravesical BCG, revealed higher expression of immune exhaustion-associated proteins within the tumor-adjacent TLSs in both responders and non-responders. Chronic local inflammation, induced by the N-butyl-N-(4-hydroxybutyl) nitrosamine carcinogen, led to TLS formation with recruitment and differentiation of the immunosuppressive atypical B-cell (ABC) subset within the bladder microenvironment, predominantly in aging female mice compared to their male counterparts. Depletion of ABCs simultaneous to BCG treatment delayed cancer progression in female mice. Our findings provide evidence indicating a role for ABCs in BCG response and will inform future development of therapies targeting the B-cell-exhaustion axis.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1320-1339"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmenting CAR T-cell Functions with LIGHT.","authors":"Winson Cai, Kento Tanaka, Xiaoli Mi, Vinagolu K Rajasekhar, Jonathan F Khan, Sarah Yoo, Elisa de Stanchina, Jahan Rahman, Serena Mathew, Parwiz Abrahimi, Sydney Souness, Terence J Purdon, James R McDowell, Jeremy Meyerberg, Takeshi Fujino, John H Healey, Omar Abdel-Wahab, David A Scheinberg, Renier J Brentjens, Anthony F Daniyan","doi":"10.1158/2326-6066.CIR-24-0246","DOIUrl":"10.1158/2326-6066.CIR-24-0246","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success in the treatment of B-cell malignancies. However, its clinical efficacy in solid tumors is limited, primarily by target antigen heterogeneity. To overcome antigen heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand of both lymphotoxin-β receptor on cancer cells and herpes virus entry mediator on immune cells. LIGHT-expressing CAR T cells displayed both antigen-directed cytotoxicity mediated by the CAR and antigen-independent killing mediated through the interaction of LIGHT with lymphotoxin-β receptor on cancer cells. Moreover, CAR T cells expressing LIGHT had immunostimulatory properties that improved the cells' proliferation and cytolytic profile. These data indicate that LIGHT-expressing CAR T cells may provide a way to eliminate antigen-negative tumor cells to prevent antigen-negative disease relapse.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1361-1379"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MR1 Gene and Protein Expression Are Enhanced by Inhibition of the Extracellular Signal-Regulated Kinase ERK.","authors":"Daniel Constantin, Vladimir Nosi, Natalie Kehrer, Alessandro Vacchini, Andrew Chancellor, Emmanuel Contassot, Aisha Beshirova, Gennaro Prota, Alexander Navarini, Lucia Mori, Gennaro De Libero","doi":"10.1158/2326-6066.CIR-24-0110","DOIUrl":"10.1158/2326-6066.CIR-24-0110","url":null,"abstract":"<p><p>The MHC class I-related molecule MR1 is ubiquitously expressed, is highly conserved among mammals, and presents bacterial and endogenous antigens in tumor cells. These features indicate that tumor-specific T cells restricted to MR1 may represent ideal candidates for novel cancer-directed T-cell immunotherapy. The very low expression of the MR1 protein at the cell surface is a potential challenge limiting the possible use of MR1-directed immunotherapies. To overcome this challenge, it is important that understanding of the mechanisms regulating MR1 expression is increased, as little is known about this currently. This study identified ERK1/2 as negative regulators of the MR1 gene and protein expression. Inhibition of ERK1/2 in tumor cells or treatment of BRAF-mutant tumor cells with drugs specific for mutated BRAF increased MR1 protein expression and recognition by tumor-reactive and MR1-restricted T cells. The ERK1/2 inhibition of MR1 was mediated by the ELF1 transcription factor, which was required for MR1 gene expression. The effects of ERK1/2 inhibition also occurred in cancer cell lines of different tissue origins, cancer cell lines resistant to drugs that inhibit mutated BRAF, and primary cancer cells, making them potential targets of specific T cells. In contrast to tumor cells, the recognition of healthy cells was very poor or absent after ERK1/2 inhibition. These findings suggest a pharmaceutical approach to increase MR1 protein expression in tumor cells and the subsequent activation of MR1-restricted T cells, and they have potential therapeutic implications.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1452-1467"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NK Receptor Signaling Lowers TCR Activation Threshold, Enhancing Selective Recognition of Cancer Cells by TAA-Specific CTLs.","authors":"Bowen Dong, Nataša Obermajer, Takemasa Tsuji, Junko Matsuzaki, Cindy M Bonura, Cindy Sander, Henry Withers, Mark D Long, Colin Chavel, Scott H Olejniczak, Hans Minderman, John M Kirkwood, Robert P Edwards, Walter J Storkus, Pedro Romero, Pawel Kalinski","doi":"10.1158/2326-6066.CIR-24-0061","DOIUrl":"10.1158/2326-6066.CIR-24-0061","url":null,"abstract":"<p><p>Cytotoxic CD8+ T lymphocyte (CTL) recognition of non-mutated tumor-associated antigens (TAA), present on cancer cells and also in healthy tissues, is an important element of cancer immunity, but the mechanism of its selectivity for cancer cells and opportunities for its enhancement remain elusive. In this study, we found that CTL expression of the NK receptors (NKR) DNAM1 and NKG2D was associated with the effector status of CD8+ tumor-infiltrating lymphocytes and long-term survival of patients with melanoma. Using MART1 and NY-ESO-1 as model TAAs, we demonstrated that DNAM1 and NKG2D regulate T-cell receptor (TCR) functional avidity and set the threshold for TCR activation of human TAA-specific CTLs. Superior co-stimulatory effects of DNAM1 over CD28 involved enhanced TCR signaling, CTL killer function, and polyfunctionality. Double transduction of human CTLs with TAA-specific TCR and NKRs resulted in strongly enhanced antigen sensitivity, without a reduction in antigen specificity and selectivity of killer function. In addition, the elevation of NKR ligand expression on cancer cells due to chemotherapy also increased CTL recognition of cancer cells expressing low levels of TAAs. Our data help explain the ability of self-antigens to mediate tumor rejection in the absence of autoimmunity and support the development of dual-targeting adoptive T-cell therapies that use NKRs to enhance the potency and selectivity of recognition of TAA-expressing cancer cells.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1421-1437"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}