Cancer immunology, immunotherapy : CII最新文献

{"title":"Naringenin potentiates anti-tumor immunity against oral cancer by inducing lymph node CD169-positive macrophage activation and cytotoxic T cell infiltration.","authors":"Sho Kawaguchi,&nbsp;Kenta Kawahara,&nbsp;Yukio Fujiwara,&nbsp;Koji Ohnishi,&nbsp;Cheng Pan,&nbsp;Hiromu Yano,&nbsp;Akiyuki Hirosue,&nbsp;Masashi Nagata,&nbsp;Masatoshi Hirayama,&nbsp;Junki Sakata,&nbsp;Hikaru Nakashima,&nbsp;Hidetaka Arita,&nbsp;Keisuke Yamana,&nbsp;Shunsuke Gohara,&nbsp;Yuka Nagao,&nbsp;Manabu Maeshiro,&nbsp;Asuka Iwamoto,&nbsp;Mayumi Hirayama,&nbsp;Ryoji Yoshida,&nbsp;Yoshihiro Komohara,&nbsp;Hideki Nakayama","doi":"10.1007/s00262-022-03149-w","DOIUrl":"https://doi.org/10.1007/s00262-022-03149-w","url":null,"abstract":"<p><p>The CD169⁺ macrophages in lymph nodes are implicated in cytotoxic T lymphocyte (CTL) activation and are associated with improved prognosis in several malignancies. Here, we investigated the significance of CD169⁺ macrophages in oral squamous cell carcinoma (OSCC). Further, we tested the anti-tumor effects of naringenin, which has been previously shown to activate CD169⁺ macrophages, in a murine OSCC model. Immunohistochemical analysis for CD169 and CD8 was performed on lymph node and primary tumor specimens from 89 patients with OSCC. We also evaluated the effects of naringenin on two murine OSCC models. Increased CD169⁺ macrophage counts in the regional lymph nodes correlated with favorable prognosis and CD8⁺ cell counts within tumor sites. Additionally, naringenin suppressed tumor growth in two murine OSCC models. The mRNA levels of CD169, interleukin (IL)-12, and C-X-C motif chemokine ligand 10 (CXCL10) in lymph nodes and CTL infiltration in tumors significantly increased following naringenin administration in tumor-bearing mice. These results suggest that CD169⁺ macrophages in lymph nodes are involved in T cell-mediated anti-tumor immunity and could be a prognostic marker for patients with OSCC. Moreover, naringenin is a new potential agent for CD169⁺ macrophage activation in OSCC treatment.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"2127-2139"},"PeriodicalIF":5.8,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39693768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression.","authors":"A Filippone,&nbsp;M Lanza,&nbsp;D Mannino,&nbsp;G Raciti,&nbsp;C Colarossi,&nbsp;D Sciacca,&nbsp;S Cuzzocrea,&nbsp;I Paterniti","doi":"10.1007/s00262-021-03130-z","DOIUrl":"https://doi.org/10.1007/s00262-021-03130-z","url":null,"abstract":"<p><p>Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell checkpoint and plays a central role in regulating T cell collapse. The binding of PD-1 to its ligand programmed death-ligand 1 (PD-L1) activates downstream signaling pathways and inhibits T cell activation in the perspective of immune system mechanism and regulation in tumor progression. It is well reported that tumors adopt certain immune-checkpoint pathways as a mechanism of resistance against immune cells such as T cells that are specific for tumor antigens. Indeed, the PD-1/PD-L1 pathway controls the induction and maintenance of immune tolerance within the tumor microenvironment. Thus, the PD-1/PD-L1 checkpoint regulation appears to be of extreme importance as well as the immunotherapy targeting that via and the using of PD-1/PD-L1 inhibitors that have changed the scenario of brain cancer treatment and survival. Here, we review the mechanism of action of PD-1 and PD-L1, the PD/PDL-1 signaling pathway involved in the progression of brain tumors, and its application as cancer immunotherapy counteracting tumor escape in central nervous system.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"2067-2075"},"PeriodicalIF":5.8,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39746395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The multitargeted receptor tyrosine kinase inhibitor sunitinib induces resistance of HER2 positive breast cancer cells to trastuzumab-mediated ADCC.","authors":"Eliza Guti,&nbsp;Zsolt Regdon,&nbsp;Isotta Sturniolo,&nbsp;Alexandra Kiss,&nbsp;Katalin Kovács,&nbsp;Máté Demény,&nbsp;Árpád Szöőr,&nbsp;György Vereb,&nbsp;János Szöllősi,&nbsp;Csaba Hegedűs,&nbsp;Zsuzsanna Polgár,&nbsp;László Virág","doi":"10.1007/s00262-022-03146-z","DOIUrl":"https://doi.org/10.1007/s00262-022-03146-z","url":null,"abstract":"<p><p>Despite recent advances in the development of novel personalized therapies, breast cancer continues to challenge physicians with resistance to various advanced therapies. The anticancer action of the anti-HER2 antibody, trastuzumab, involves antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells. Here, we report a repurposing screen of 774 clinically used compounds on NK-cell + trastuzumab-induced killing of JIMT-1 breast cancer cells. Using a calcein-based high-content screening (HCS) assay for the image-based quantitation of ADCC that we have developed and optimized for this purpose, we have found that the multitargeted tyrosine kinase inhibitor sunitinib inhibits ADCC in this model. The cytoprotective effect of sunitinib was also confirmed with two other assays (lactate dehydrogenase release, and electric cell substrate impedance sensing, ECIS). The drug suppressed NK cell activation as indicated by reduced granzyme B deposition on to the target cells and inhibition of interferon-γ production by the NK cells. Moreover, sunitinib induced downregulation of HER2 on the target cells' surface, changed the morphology and increased adherence of the target cells. Moreover, sunitinib also triggered the autophagy pathway (speckled LC3b) as an additional potential underlying mechanism of the cytoprotective effect of the drug. Sunitinib-induced ADCC resistance has been confirmed in a 3D tumor model revealing the prevention of apoptotic cell death (Annexin V staining) in JIMT-1 spheroids co-incubated with NK cells and trastuzumab. In summary, our HCS assay may be suitable for the facile identification of ADCC boosting compounds. Our data urge caution concerning potential combinations of ADCC-based immunotherapies and sunitinib.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"2151-2168"},"PeriodicalIF":5.8,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39849773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of characteristics and tumor targeting properties of extracellular vesicles derived from primary NK cells or NK-cell lines stimulated with IL-15 or IL-12/15/18.","authors":"Miriam Aarsund,&nbsp;Filip M Segers,&nbsp;Yunjie Wu,&nbsp;Marit Inngjerdingen","doi":"10.1007/s00262-022-03161-0","DOIUrl":"https://doi.org/10.1007/s00262-022-03161-0","url":null,"abstract":"<p><p>NK cell-based therapies have shown promise for hematological cancer forms, but their use against solid tumors is hampered by their poor ability to infiltrate the tumor. NK cells release extracellular vesicles (EVs) containing cytolytic proteins, indicating that NK-cell derived EVs may have therapeutic potential. In this study, we compared the tumor-targeting potential of EVs derived from either primary NK cells or the NK cell lines NK-92 and KHYG-1 cultured in IL-15 alone or in combination with IL-12 and IL-18. Primary NK cells were also stimulated through the activating receptor CD16. Tumor cell apoptosis was measured using a panel of human colon, melanoma, glioblastoma, prostate, breast, and ovarian tumor cell line spheroids. NK cells or NK-92 cells stimulated with IL-12, IL-15, and IL-18 generated EVs with higher efficiency than EVs from resting cells, although similar amounts of EVs were produced under both conditions. Proteomic analysis indicated similar distribution of cytolytic proteins in EVs from primary NK cells and NK-92, but lower levels in KHYG-1 EVs that translated into poor capacity for KHYG-1 EVs at targeting tumor cell lines. Further, we show that CD16-stimulated NK cells release low amounts of EVs devoid of cytolytic proteins. Importantly, EVs from cytokine-stimulated NK cells penetrate into the spheroid core, and tumor spheroid susceptibility to NK-cell derived EVs was linked to differential expression of the NKG2D ligands MICA/B, which was blocked with an anti-NKG2D antibody. We conclude that EVs from activated primary NK cells or NK-92 cells has the best potential to infiltrate and target solid tumors.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"2227-2238"},"PeriodicalIF":5.8,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39765877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blocking GARP-mediated activation of TGF-β1 did not alter innate or adaptive immune responses to bacterial infection or protein immunization in mice.","authors":"Mélanie Gaignage,&nbsp;Xuhao Zhang,&nbsp;Julie Stockis,&nbsp;Olivier Dedobbeleer,&nbsp;Camille Michiels,&nbsp;Perrine Cochez,&nbsp;Laure Dumoutier,&nbsp;Pierre G Coulie,&nbsp;Sophie Lucas","doi":"10.1007/s00262-021-03119-8","DOIUrl":"https://doi.org/10.1007/s00262-021-03119-8","url":null,"abstract":"<p><p>Transmembrane protein GARP binds latent TGF-β1 to form GARP:(latent)TGF-β1 complexes on the surface of several cell types including Tregs, B-cells, and platelets. Upon stimulation, these cells release active TGF-β1. Blocking TGF-β1 activation by Tregs with anti-GARP:TGF-β1 mAbs overcomes resistance to PD1/PD-L1 blockade and induces immune-mediated regressions of murine tumors, indicating that Treg-derived TGF-β1 inhibits anti-tumor immunity. TGF-β1 exerts a vast array of effects on immune responses. For example, it favors differentiation of T_H17 cells and B-cell switch to IgA production, two important processes for mucosal immunity. Here, we sought to determine whether treatment with anti-GARP:TGF-β1 mAbs would perturb immune responses to intestinal bacterial infection. We observed no aggravation of intestinal disease, no systemic dissemination, and no alteration of innate or adaptative immune responses upon oral gavage of C. rodentium in highly susceptible Il22r^-/- mice treated with anti-GARP:TGF-β1 mAbs. To examine the effects of GARP:TGF-β1 blockade on Ig production, we compared B cell- and T_H cell- responses to OVA or CTB protein immunization in mice carrying deletions of Garp in Tregs, B cells, or platelets. No alteration of adaptive immune responses to protein immunization was observed in the absence of GARP on any of these cells. Altogether, we show that antibody-mediated blockade of GARP:TGF-β1 or genetic deletion of Garp in Tregs, B cells or platelets, do not alter innate or adaptive immune responses to intestinal bacterial infection or protein immunization in mice. Anti-GARP:TGF-β1 mAbs, currently tested for cancer immunotherapy, may thus restore anti-tumor immunity without severely impairing other immune defenses. PRéCIS: Immunotherapy with GARP:TGF-β1 mAbs may restore anti-tumor immunity without impairing immune or inflammatory responses required to maintain homeostasis or host defense against infection, notably at mucosal barriers.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"1851-1862"},"PeriodicalIF":5.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39777319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional virus-specific memory T cells survey glioblastoma.","authors":"Jianfang Ning,&nbsp;Noah V Gavil,&nbsp;Shaoping Wu,&nbsp;Sathi Wijeyesinghe,&nbsp;Eyob Weyu,&nbsp;Jun Ma,&nbsp;Ming Li,&nbsp;Florina-Nicoleta Grigore,&nbsp;Sanjay Dhawan,&nbsp;Alexander G J Skorput,&nbsp;Shawn C Musial,&nbsp;Clark C Chen,&nbsp;David Masopust,&nbsp;Pamela C Rosato","doi":"10.1007/s00262-021-03125-w","DOIUrl":"https://doi.org/10.1007/s00262-021-03125-w","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is among the most aggressive, treatment-resistant cancers, and despite standard of care surgery, radiation and chemotherapy, is invariably fatal. GBM is marked by local and systemic immunosuppression, contributing to resistance to existing immunotherapies that have had success in other tumor types. Memory T cells specific for previous infections reside in tissues throughout the host and are capable of rapid and potent immune activation. Here, we show that virus-specific memory CD8 + T cells expressing tissue-resident markers populate the mouse and human glioblastoma microenvironment. Reactivating virus-specific memory T cells through intratumoral delivery of adjuvant-free virus-derived peptide triggered local immune activation. This delivery translated to antineoplastic effects, which improved survival in a murine glioblastoma model. Our results indicate that virus-specific memory T cells are a significant part of the glioblastoma immune microenvironment and may be leveraged to promote anti-tumoral immunity.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"1863-1875"},"PeriodicalIF":5.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271132/pdf/nihms-1802396.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39675540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase I dose-escalation, safety/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma.","authors":"Eiji Kiyohara,&nbsp;Atsushi Tanemura,&nbsp;Kazuma Sakura,&nbsp;Toshihiro Nakajima,&nbsp;Akira Myoui,&nbsp;Naoya Yamazaki,&nbsp;Yoshio Kiyohara,&nbsp;Ichiro Katayama,&nbsp;Manabu Fujimoto,&nbsp;Yasufumi Kaneda","doi":"10.1007/s00262-021-03122-z","DOIUrl":"https://doi.org/10.1007/s00262-021-03122-z","url":null,"abstract":"<p><p>Despite recent advance in immunotherapy agents, safe new therapies that enhance the effects of immune checkpoint inhibitors are still required to develop. We previously demonstrated that hemagglutinating virus of Japan-envelope (HVJ-E) induced not only direct tumor cell death but also antitumor immunity through the activation of T and natural killer (NK) cells, thereafter, developed a manufacturing process of HVJ-E (GEN0101) for clinical use. We here performed a phase Ia clinical trial of intratumoral GEN0101 administration in six patients with stage IIIC or IV malignant melanoma. The primary aim was to evaluate the safety and tolerability of GEN0101, and the secondary aim was to examine the objective tumor response. Patients were separated into two groups (n = 3 each) and received a low dose of 30,000 and high dose of 60,000 mNAU of GEN0101. All patients completed a two-week follow-up evaluation without severe adverse events. The overall response rate was 33% (2 of 6), with 2 partial responses in the high-dose group and 2 with stable disease, and 2 with progressive disease in the low-dose group. Local complete or partial responses were observed in 11 of 18 (61%) target lesions. One patient demonstrated shrinkage of lung metastases after the treatment. The activity of NK cells and interferon-γ levels were increased in the circulation, indicating augmentation of antitumor immunity by GEN0101. This trial showed not only the safety and tolerability but also the significant antitumor effect of GEN0101, suggesting that GEN0101 might be a promising new drug for patients with advanced melanoma.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"2041-2049"},"PeriodicalIF":5.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39898442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-related adverse events of COVID-19 vaccination in skin cancer patients receiving immune-checkpoint inhibitor treatment.","authors":"Sophia B Strobel,&nbsp;Devayani Machiraju,&nbsp;Katharina A Kälber,&nbsp;Jessica C Hassel","doi":"10.1007/s00262-021-03133-w","DOIUrl":"https://doi.org/10.1007/s00262-021-03133-w","url":null,"abstract":"<p><p>To date, few data are available regarding Adverse events (AEs) in cancer patients who are vaccinated for coronavirus disease 2019 (COVID-19) while being actively treated with Immune-checkpoint inhibitors (ICIs). We aimed to assess the safety of COVID-19 vaccines approved in Germany. Specifically, we investigated the frequency of general side effects and immune-related AEs of COVID-19 vaccination. A triage survey was used to collect the following information for patients with metastatic skin cancer: vaccine type, date of receipt of each dose of vaccine, and self-reported side effects. Clinical data were retrieved from the patients' medical records. Of 130 patients with metastatic skin cancer, 89 patients were on immunotherapy and received COVID-19 vaccination. Of these 89 patients (median age: 64 years; 57 [64%] men), 89% had melanoma, and 71% received ICI therapy with a PD-1 antibody. Eighty-eight percent received an mRNA-based COVID-19 vaccination. The median follow-up time was 125 days after the first vaccination, and 84 days after the second. The most common observed side effects were mild to moderate pain at the injection site (40%), followed by fatigue (24%). Grade 3 irAEs were reported in eight patients, seven of whom were on nivolumab plus ipilimumab combination treatment. Of the 19 patients vaccinated within 72 h before/after ICI, five developed irAEs within 17 days (1-17 days). This small cohort study suggests that approved COVID-19 vaccinations are safe for use in cancer patients receiving ICIs. However, some precautions should be taken, especially regarding the timing of vaccination and ICI treatment.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"2051-2056"},"PeriodicalIF":5.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39752012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden.","authors":"Julia Femel,&nbsp;Luuk van Hooren,&nbsp;Melanie Herre,&nbsp;Jessica Cedervall,&nbsp;Falk Saupe,&nbsp;Elisabeth J M Huijbers,&nbsp;Danielle R J Verboogen,&nbsp;Matthias Reichel,&nbsp;Victor L Thijssen,&nbsp;Arjan W Griffioen,&nbsp;Lars Hellman,&nbsp;Anna Dimberg,&nbsp;Anna-Karin Olsson","doi":"10.1007/s00262-021-03139-4","DOIUrl":"https://doi.org/10.1007/s00262-021-03139-4","url":null,"abstract":"<p><p>Galectin-1 (Gal1) is a glycan-binding protein that promotes tumor progression by several distinct mechanisms. Through direct binding to vascular endothelial growth factor (VEGF)-receptor 2, Gal1 is able to induce VEGF-like signaling, which contributes to tumor angiogenesis. Furthermore, several studies have demonstrated an immunosuppressive function of Gal1 through effects on both effector and regulatory T cells. Elevated Gal1 expression and secretion have been shown in many tumor types, and high Gal1 serum levels have been connected to poor prognosis in cancer patients. These findings suggest that therapeutic strategies directed against Gal1 would enable simultaneous targeting of angiogenesis, immune evasion and metastasis. In the current study, we have analyzed the potential of Gal1 as a cancer vaccine target. We show that it is possible to generate high anti-Gal1 antibody levels in mice immunized with a recombinant vaccine protein consisting of bacterial sequences fused to Gal1. Growth of Gal1 expressing melanomas was significantly impaired in the immunized mice compared to the control group. This was associated with improved perfusion of the tumor vasculature, as well as increased infiltration of macrophages and cytotoxic T cells (CTLs). The level of granzyme B, mainly originating from CTLs in our model, was significantly elevated in Gal1 vaccinated mice and correlated with a decrease in tumor burden. We conclude that vaccination against Gal1 is a promising pro-immunogenic approach for cancer therapy that could potentially enhance the effect of other immunotherapeutic strategies due to its ability to promote CTL influx in tumors.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"2029-2040"},"PeriodicalIF":5.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39812942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local radiotherapy and E7 RNA-LPX vaccination show enhanced therapeutic efficacy in preclinical models of HPV16⁺ cancer.","authors":"Nadja Salomon,&nbsp;Abderaouf Selmi,&nbsp;Christian Grunwitz,&nbsp;Anthony Kong,&nbsp;Eliana Stanganello,&nbsp;Jennifer Neumaier,&nbsp;Jutta Petschenka,&nbsp;Mustafa Diken,&nbsp;Sebastian Kreiter,&nbsp;Özlem Türeci,&nbsp;Ugur Sahin,&nbsp;Fulvia Vascotto","doi":"10.1007/s00262-021-03134-9","DOIUrl":"https://doi.org/10.1007/s00262-021-03134-9","url":null,"abstract":"<p><p>Human papilloma virus (HPV) infection is a causative agent for several cancers types (genital, anal and head and neck region). The HPV E6 and E7 proteins are oncogenic drivers and thus are ideal candidates for therapeutic vaccination. We recently reported that a novel ribonucleic acid lipoplex (RNA-LPX)-based HPV16 vaccine, E7 RNA-LPX, mediates regression of mouse HPV16⁺ tumors and establishes protective T cell memory. An HPV16 E6/E7 RNA-LPX vaccine is currently being investigated in two phase I and II clinical trials in various HPV-driven cancer types; however, it remains a high unmet medical need for treatments for patients with radiosensitive HPV16⁺ tumors. Therefore, we set out to investigate the therapeutic efficacy of E7 RNA-LPX vaccine combined with standard-of-care local radiotherapy (LRT). We demonstrate that E7 RNA-LPX synergizes with LRT in HPV16⁺ mouse tumors, with potent therapeutic effects exceeding those of either monotherapy. Mode of action studies revealed that the E7 RNA-LPX vaccine induced high numbers of intratumoral-E7-specific CD8⁺ T cells, rendering cold tumors immunologically hot, whereas LRT primarily acted as a cytotoxic therapy, reducing tumor mass and intratumor hypoxia by predisposing tumor cells to antigen-specific T cell-mediated killing. Overall, LRT enhanced the effector function of E7 RNA-LPX-primed T cell responses. The therapeutic synergy was dependent on total radiation dose, rather than radiation dose-fractionation. Together, these results show that LRT synergizes with E7 RNA-LPX and enhances its anti-tumor activity against HPV16⁺ cancer models. This work paves into a new translational therapy for HPV16⁺ cancer patients.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"1975-1988"},"PeriodicalIF":5.8,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39636647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}