Neoadjuvant sipuleucel-T induces both Th1 activation and immune regulation in localized prostate cancer.

Abstract:

:Sipuleucel-T is the only FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. The mechanism by which this treatment improves survival is not fully understood. We have previously shown that this treatment can induce the recruitment of CD4 and CD8 T cells to the tumor microenvironment. In this study, we examined the functional state of these T cells through gene expression profiling. We found that the magnitude of T cell signatures correlated with the frequency of T cells as measured by immunohistochemistry. Sipuleucel-T treatment was associated with increased expression of Th1-associated genes, but not Th2-, Th17 - or Treg-associated genes. Post-treatment tumor tissues with high CD8+T cell infiltration was associated with high levels of CXCL10 expression. On in situ hybridization, CXCL10+ cells colocalized with CD8+T cells in post-treatment prostatectomy tumor tissue. Neoadjuvant sipuleucel-T was also associated with upregulation of immune inhibitory checkpoints, including CTLA4 and TIGIT, and downregulation of the immune activation marker, dipeptidylpeptidase, DPP4. Treatment-associated declines in serum PSA were correlated with induction of Th1 response. In contrast, rises in serum PSA while on treatment were associated with the induction of multiple immune checkpoints, including CTLA4, CEACAM6 and TIGIT. This could represent adaptive immune resistance mechanisms induced by treatment. Taken together, neoadjuvant sipuleucel-T can induce both a Th1 response and negative immune regulation in the prostate cancer microenvironment.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Hagihara K,Chan S,Zhang L,Oh DY,Wei XX,Simko J,Fong L

doi

10.1080/2162402X.2018.1486953

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

e1486953

issue

1

eissn

2162-4011

issn

2162-402X

pii

1486953

journal_volume

8

pub_type

杂志文章
  • Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma.

    abstract::Efforts to reduce immunosuppression in the solid tumor microenvironment by blocking the recruitment or polarization of tumor associated macrophages (TAM), or myeloid derived suppressor cells (MDSCs), have gained momentum in recent years. Expanding our knowledge of the immune cell types, cytokines, or recruitment facto...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1507668

    authors: Moyes KW,Davis A,Hoglund V,Haberthur K,Lieberman NA,Kreuser SA,Deutsch GH,Franco S,Locke D,Carleton MO,Gilbertson DG,Simmons R,Winter C,Silber J,Gonzalez-Cuyar LF,Ellenbogen RG,Crane CA

    更新日期:2018-08-27 00:00:00

  • A perspective on new immune adjuvant principles: Reprogramming inflammatory states to permit clearance of cancer cells and other age-associated cellular pathologies.

    abstract::Aging entails the accumulation of neoantigens comprised of aggregated, oxidized, mutated and misfolded biomolecules, including advanced-glycation end projects (AGEs). There is evidence that the immune system can recognize and clear cells fouled by these molecular debris, which contribute to the emergence of cancer and...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21358

    authors: Prendergast GC,Metz R

    更新日期:2012-09-01 00:00:00

  • Overcoming immunosuppression to enhance a p53MVA vaccine.

    abstract::A Phase I trial of a p53-targeting modified vaccinia Ankara (p53MVA) vaccine in patients afflicted with refractory gastrointestinal cancers demonstrated enhanced T-cell recognition of p53 following vaccination. However, this effect was transient suggesting that p53MVA requires combination with immunomodulatory agents ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.958949

    authors: Hardwick N,Chung V,Cristea M,Ellenhorn JD,Diamond DJ

    更新日期:2014-12-15 00:00:00

  • The extent to which melanoma alters tissue-resident dendritic cell function correlates with tumorigenicity.

    abstract::We have shown that melanoma-derived factors alter the function of differentiated tissue-resident dendritic cells (DC) in a tumorigenicity-dependent manner. Soluble factors, including TGFβ1 and VEGF-A, contributed to dendritic cell dysfunction associated with a highly-aggressive melanoma and conferred a phenotype upon ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1069462

    authors: Hargadon KM

    更新日期:2015-08-12 00:00:00

  • Extracellular HSP110 skews macrophage polarization in colorectal cancer.

    abstract::HSP110 is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps the cells to survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently showed that colorectal cancer (CRC) patients with microsatellite instability (MSI) had an improved r...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1170264

    authors: Berthenet K,Boudesco C,Collura A,Svrcek M,Richaud S,Hammann A,Causse S,Yousfi N,Wanherdrick K,Duplomb L,Duval A,Garrido C,Jego G

    更新日期:2016-04-22 00:00:00

  • A pipeline for identification and validation of tumor-specific antigens in a mouse model of metastatic breast cancer.

    abstract::Cancer immunotherapy continues to make headway as a treatment for advanced stage tumors, revealing an urgent need to understand the fundamentals of anti-tumor immune responses. Noteworthy is a scarcity of data pertaining to the breadth and specificity of tumor-specific T cell responses in metastatic breast cancer. Aut...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1685300

    authors: DeVette CI,Gundlapalli H,Lai SA,McMurtrey CP,Hoover AR,Gurung HR,Chen WR,Welm AL,Hildebrand WH

    更新日期:2019-11-29 00:00:00

  • Trial watch: Dendritic cell-based anticancer immunotherapy.

    abstract::Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2017.1328341

    authors: Garg AD,Vara Perez M,Schaaf M,Agostinis P,Zitvogel L,Kroemer G,Galluzzi L

    更新日期:2017-05-12 00:00:00

  • Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer.

    abstract::Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1380764

    authors: Priceman SJ,Gerdts EA,Tilakawardane D,Kennewick KT,Murad JP,Park AK,Jeang B,Yamaguchi Y,Yang X,Urak R,Weng L,Chang WC,Wright S,Pal S,Reiter RE,Wu AM,Brown CE,Forman SJ

    更新日期:2017-10-16 00:00:00

  • Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice.

    abstract::Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated p...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1320009

    authors: Cedervall J,Dragomir A,Saupe F,Zhang Y,Ärnlöv J,Larsson E,Dimberg A,Larsson A,Olsson AK

    更新日期:2017-04-20 00:00:00

  • ATM activation mediates anticancer immunosurveillance by natural killer and T cells.

    abstract::The DNA damage response (DDR), which is frequently activated in cancer cells, has been proposed to operate as an early barrier against oncogenesis. We have recently shown that ATM mediates the spontaneous regression of Eμ-myc-driven murine B-cell leukemia in a natural killer and T cell-dependent manner. The DDR partia...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.24438

    authors: Tang ML,Gasser S

    更新日期:2013-06-01 00:00:00

  • Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition.

    abstract::High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTE...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1264565

    authors: Eggink FA,Van Gool IC,Leary A,Pollock PM,Crosbie EJ,Mileshkin L,Jordanova ES,Adam J,Freeman-Mills L,Church DN,Creutzberg CL,De Bruyn M,Nijman HW,Bosse T

    更新日期:2016-12-09 00:00:00

  • High sensitivity of cancer exome-based CD8 T cell neo-antigen identification.

    abstract::Recent data suggest that T-cell reactivity against tumor-specific neo-antigens may be central to the clinical efficacy of cancer immunotherapy. The development of personalized vaccines designed to boost T-cell reactivity against patient specific neo-antigens has been proposed largely on the basis of these findings. Wo...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.28836

    authors: van Buuren MM,Calis JJ,Schumacher TN

    更新日期:2014-05-14 00:00:00

  • Autochthonous T cells to the rescue: IL-10 directly activates tumor-resident CD8(+) T cells.

    abstract::Successful cancer immunotherapy is thought to require de novo priming of tumor specific CD8(+) T cells in lymphatic organs. Contrasting these beliefs, cancer therapy based on interleukin-10 (IL-10) results in tumor rejection without a requirement for T-cell trafficking from lymphatic organs. Rather, IL-10 directly act...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.21683

    authors: Emmerich J,Mumm JB,Oft M

    更新日期:2012-12-01 00:00:00

  • TIGIT blockade enhances functionality of peritoneal NK cells with altered expression of DNAM-1/TIGIT/CD96 checkpoint molecules in ovarian cancer.

    abstract::Advanced ovarian cancer (OC) patients have a poor 5-year survival of only 28%, emphasizing the medical need for improved therapies. Adjuvant immunotherapy could be an attractive approach since OC is an immunogenic disease and the presence of tumor-infiltrating lymphocytes has shown to positively correlate with patient...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1843247

    authors: Maas RJ,Hoogstad-van Evert JS,Van der Meer JM,Mekers V,Rezaeifard S,Korman AJ,de Jonge PK,Cany J,Woestenenk R,Schaap NP,Massuger LF,Jansen JH,Hobo W,Dolstra H

    更新日期:2020-11-08 00:00:00

  • A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes.

    abstract::The tumor microenvironment is characterized by of high levels of extracellular nucleotides that are metabolized through the dynamic and sequential action of cell surface enzymes (ectoenzymes). These ectoenzymes operate according to their spatial arrangement, as part of (1) continuous (molecules on the same cell) or (2...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.26246

    authors: Horenstein AL,Chillemi A,Zaccarello G,Bruzzone S,Quarona V,Zito A,Serra S,Malavasi F

    更新日期:2013-09-01 00:00:00

  • Metformin blocks myeloid-derived suppressor cell accumulation through AMPK-DACH1-CXCL1 axis.

    abstract::Purpose: Tumor development has been closely linked to tumor microenvironment, particularly in terms of myeloid-derived suppressive cells (MDSCs), a heterogeneous population of immature myeloid cells that protect tumors from elimination by immune cells. Approaches aimed at blocking MDSC accumulation could improve cance...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1442167

    authors: Qin G,Lian J,Huang L,Zhao Q,Liu S,Zhang Z,Chen X,Yue D,Li L,Li F,Wang L,Umansky V,Zhang B,Yang S,Zhang Y

    更新日期:2018-03-13 00:00:00

  • Targeting the C-terminus of galectin-9 induces mesothelioma apoptosis and M2 macrophage depletion.

    abstract::Galectin-9 has emerged as a promising biological target for cancer immunotherapy due to its role as a regulator of macrophage and T-cell differentiation. In addition, its expression in tumor cells modulates tumor cell adhesion, metastasis, and apoptosis. Malignant mesothelioma (MM) is an aggressive neoplasm of the mes...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2019.1601482

    authors: Bertino P,Premeaux TA,Fujita T,Haun BK,Marciel MP,Hoffmann FW,Garcia A,Yiang H,Pastorino S,Carbone M,Niki T,Berestecky J,Hoffmann PR,Ndhlovu LC

    更新日期:2019-04-17 00:00:00

  • Cell-type specific MyD88 signaling is required for intestinal tumor initiation and progression to malignancy.

    abstract::The signal adapter MyD88, an essential component of Toll-like receptor (TLR) signaling, is important for gut-microbiome interactions. However, its contribution to cancer and its cell-type specific functions are controversially discussed. Therefore, we generated new tissue-specific mouse models and analyzed the clinica...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2018.1466770

    authors: Holtorf A,Conrad A,Holzmann B,Janssen KP

    更新日期:2018-06-11 00:00:00

  • NK cells sense tumors, course of disease and treatments: Consequences for NK-based therapies.

    abstract::The recent findings on NK activation indicate that these cells are important antitumor effectors. NK cells participate in the graft-vs.-leukemia effect to control the relapse in leukemic patients transplanted with allogeneic hematopoietic stem cells. In various tumors, correlation between NK cell infiltrates and progn...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.1.1.18312

    authors: Fregni G,Perier A,Avril MF,Caignard A

    更新日期:2012-01-01 00:00:00

  • Blockade of only TGF-β 1 and 2 is sufficient to enhance the efficacy of vaccine and PD-1 checkpoint blockade immunotherapy.

    abstract::Checkpoint inhibition has established immunotherapy as a major modality of cancer treatment. However, the success of cancer immunotherapy is still limited as immune regulation of tumor immunity is very complicated and mechanisms involved may also differ among cancer types. Beside checkpoints, other good candidates for...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1308616

    authors: Terabe M,Robertson FC,Clark K,De Ravin E,Bloom A,Venzon DJ,Kato S,Mirza A,Berzofsky JA

    更新日期:2017-03-31 00:00:00

  • Poly(I:C) primes primary human glioblastoma cells for an immune response invigorated by PD-L1 blockade.

    abstract::Prognosis of glioblastoma remains dismal, underscoring the need for novel therapies. Immunotherapy is generating promising results, but requires combination strategies to unlock its full potential. We investigated the immunomodulatory capacities of poly(I:C) on primary human glioblastoma cells and its combinatorial po...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1407899

    authors: De Waele J,Marcq E,Van Audenaerde JR,Van Loenhout J,Deben C,Zwaenepoel K,Van de Kelft E,Van der Planken D,Menovsky T,Van den Bergh JM,Willemen Y,Pauwels P,Berneman ZN,Lardon F,Peeters M,Wouters A,Smits EL

    更新日期:2017-12-12 00:00:00

  • A Phase 1b Study Evaluating the Safety, Tolerability, and Immunogenicity of CMB305, a Lentiviral-Based Prime-Boost Vaccine Regimen, in Patients with Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1.

    abstract::Preclinical data suggest that a "prime-boost" vaccine regimen using a target-expressing lentiviral vector for priming, followed by a recombinant protein boost, may be effective against cancer; however, this strategy has not been evaluated in a clinical setting. CMB305 is a prime-boost vaccine designed to induce a broa...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2020.1847846

    authors: Somaiah N,Chawla SP,Block MS,Morris JC,Do K,Kim JW,Druta M,Sankhala KK,Hwu P,Jones RL,Gnjatic S,Kim-Schulze S,Tuballes K,Yishak M,Lu H,Yakovich A,Ter Meulen J,Chen M,Kenney RT,Bohac C,Pollack SM

    更新日期:2020-11-19 00:00:00

  • Th1 epitope selection for clinically effective cancer vaccines.

    abstract::New cancer immunotherapies mark progress in our understanding of tumor biology and harnessing the immune system's management of self. However, protein- and peptide-based vaccines are not yet consistently efficacious. Recent work uncovers principles governing the genesis of T helper type-restrictive immunity to self-an...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/21624011.2014.954971

    authors: Disis ML,Watt WC,Cecil DL

    更新日期:2014-12-13 00:00:00

  • Chronic activation of DNA damage signals causes tumor immune evasion in the chemoresistant niche.

    abstract::DNA damage responses have been proposed as a gatekeeper to block tumorigenesis. We identify unexpected mechanisms whereby ATM-mediated pathway interacts with NFκB inflammatory cascades, leading to upregulation of integrin-αbβ3 on chemoresistant tumor cells. The integrin-αbβ3 is responsible for impeding tumor-specific ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.4161/onci.19123

    authors: Jinushi M

    更新日期:2012-05-01 00:00:00

  • Producer T cells: Using genetically engineered T cells as vehicles to generate and deliver therapeutics to tumors.

    abstract::Adoptive cell transfer (ACT) is an emerging anticancer therapy that has shown promise in various malignancies. Redirecting antigen specificity by genetically engineering T cells to stably express receptors has become an effective variant of ACT. A novel extension of this approach is to utilize engineered T cells to pr...

    journal_title:Oncoimmunology

    pub_type: 杂志文章,评审

    doi:10.1080/2162402X.2015.1122158

    authors: Tsai AK,Davila E

    更新日期:2016-01-15 00:00:00

  • ATTACK, a novel bispecific T cell-recruiting antibody with trivalent EGFR binding and monovalent CD3 binding for cancer immunotherapy.

    abstract::The redirection of T cell activity using bispecific antibodies is one of the most promising cancer immunotherapy approaches currently in development, but it is limited by cytokine storm-related toxicities, as well as the pharmacokinetics and tumor-penetrating capabilities of current bispecific antibody formats. Here, ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2017.1377874

    authors: Harwood SL,Alvarez-Cienfuegos A,Nuñez-Prado N,Compte M,Hernández-Pérez S,Merino N,Bonet J,Navarro R,Van Bergen En Henegouwen PMP,Lykkemark S,Mikkelsen K,Mølgaard K,Jabs F,Sanz L,Blanco FJ,Roda-Navarro P,Alvarez-Vallina L

    更新日期:2017-09-27 00:00:00

  • Autoantibodies specific to estrogen receptor alpha act as estrogen agonists and their levels correlate with breast cancer cell proliferation.

    abstract::Estrogen receptors have recently been demonstrated at the cell surface. Unlike nuclear receptors, they are able to trigger rapid responses inside the cells. In this study, we evaluated the presence and the possible role of autoantibodies specific to estrogen receptor (anti-ER Abs) in the peripheral blood of breast can...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1074375

    authors: Maselli A,Capoccia S,Pugliese P,Raggi C,Cirulli F,Fabi A,Malorni W,Pierdominici M,Ortona E

    更新日期:2015-08-12 00:00:00

  • Cell-to-cell distances between tumor-infiltrating inflammatory cells have the potential to distinguish functionally active from suppressed inflammatory cells.

    abstract::Beyond their mere presence, the distribution pattern of inflammatory cells is of special interest. Our hypothesis was that random distribution may be a clear indicator of being non-functional as a consequence of lack of interaction. Here, we have assessed the implication of cell-to-cell distances among inflammatory ce...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2015.1127494

    authors: Nagl S,Haas M,Lahmer G,Büttner-Herold M,Grabenbauer GG,Fietkau R,Distel LV

    更新日期:2016-01-13 00:00:00

  • Ipilimumab administered to metastatic melanoma patients who progressed after dendritic cell vaccination.

    abstract:BACKGROUND:Ipilimumab has proven to be effective in metastatic melanoma patients. The purpose of this study was to determine the efficacy of ipilimumab in advanced melanoma patients who showed progressive disease upon experimental dendritic cell (DC) vaccination. METHODS:Retrospective analysis of 48 stage IV melanoma ...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1201625

    authors: Boudewijns S,Koornstra RH,Westdorp H,Schreibelt G,van den Eertwegh AJ,Geukes Foppen MH,Haanen JB,de Vries IJ,Figdor CG,Bol KF,Gerritsen WR

    更新日期:2016-06-17 00:00:00

  • The immune checkpoint ligand PD-L1 is upregulated in EMT-activated human breast cancer cells by a mechanism involving ZEB-1 and miR-200.

    abstract::PD-L1 expression and regulation by mesenchymal tumor cells remain largely undefined. Here, we report that among different EMT-activated MCF7 human breast cancer cell clones, PD-L1 was differentially upregulated in MCF7 sh-WISP2, MCF7-1001/2101, and MDA-MB-231 cells but not in MCF7 SNAI1 and MCF7 SNAI1-6SA cells. Mecha...

    journal_title:Oncoimmunology

    pub_type: 杂志文章

    doi:10.1080/2162402X.2016.1263412

    authors: Noman MZ,Janji B,Abdou A,Hasmim M,Terry S,Tan TZ,Mami-Chouaib F,Thiery JP,Chouaib S

    更新日期:2017-01-23 00:00:00