Macropinocytosis of Nab-paclitaxel Drives Macrophage Activation in Pancreatic Cancer.


:Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first-line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis. The macropinocytic uptake of nab-paclitaxel induced macrophage immunostimulatory (M1) cytokine expression and synergized with IFNγ to promote inducible nitric oxide synthase expression in a TLR4-dependent manner. Nab-paclitaxel was internalized by tumor-associated macrophages in vivo, and therapeutic doses of nab-paclitaxel alone, and in combination with gemcitabine, increased the MHCII+CD80+CD86+ M1 macrophage population. These data revealed an unanticipated role for nab-paclitaxel in macrophage activation and rationalized its potential use to target immune evasion in pancreatic cancer. Cancer Immunol Res; 5(3); 182-90. ©2017 AACR.


Cancer Immunol Res


Cullis J,Siolas D,Avanzi A,Barui S,Maitra A,Bar-Sagi D




Has Abstract


2017-03-01 00:00:00














  • Reducing Toxicity of Immune Therapy Using Aptamer-Targeted Drug Delivery.

    abstract::Modulating the function of immune receptors with antibodies is ushering in a new era in cancer immunotherapy. With the notable exception of PD-1 blockade used as monotherapy, immune modulation can be associated with significant toxicities that are expected to escalate with the development of increasingly potent immune...

    journal_title:Cancer immunology research

    pub_type: 杂志文章,评审


    authors: Gilboa E,Berezhnoy A,Schrand B

    更新日期:2015-11-01 00:00:00

  • Transfer of MicroRNA via Macrophage-Derived Extracellular Vesicles Promotes Proneural-to-Mesenchymal Transition in Glioma Stem Cells.

    abstract::Proneural-to-mesenchymal transition (PMT) is a common process in glioblastoma (GBM) progression that leads to increased radiotherapy resistance. However, the mechanism underlying PMT is poorly understood. Here, we found that tumor-associated macrophages triggered PMT in glioma stem cells (GSC) via small extracellular ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Zhang Z,Xu J,Chen Z,Wang H,Xue H,Yang C,Guo Q,Qi Y,Guo X,Qian M,Wang S,Qiu W,Gao X,Zhao R,Guo X,Li G

    更新日期:2020-07-01 00:00:00

  • CCR2-Dependent Recruitment of Tregs and Monocytes Following Radiotherapy Is Associated with TNFα-Mediated Resistance.

    abstract::Radiotherapy (RT) represents one of the main anticancer approaches for the treatment of solid tumors. Beyond the expected direct effects of RT on tumor cells, evidence supporting the importance of an immune response to RT is growing. The balance between RT-mediated immunogenic and tolerogenic activity is ill-defined a...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Mondini M,Loyher PL,Hamon P,Gerbé de Thoré M,Laviron M,Berthelot K,Clémenson C,Salomon BL,Combadière C,Deutsch E,Boissonnas A

    更新日期:2019-03-01 00:00:00

  • Treatment of Multiple Myeloma Using Chimeric Antigen Receptor T Cells with Dual Specificity.

    abstract::Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable successes in fighting B-cell leukemias/lymphomas. Promising response rates are reported in patients treated with B-cell maturation antigen (BCMA) CAR T cells for multiple myeloma. However, responses appear to be nondurable, highlighting the need to ex...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Globerson Levin A,Rawet Slobodkin M,Waks T,Horn G,Ninio-Many L,Deshet Unger N,Ohayon Y,Suliman S,Cohen Y,Tartakovsky B,Naparstek E,Avivi I,Eshhar Z

    更新日期:2020-12-01 00:00:00

  • The Clinical Activity of PD-1/PD-L1 Inhibitors in Metastatic Non-Clear Cell Renal Cell Carcinoma.

    abstract::Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have shown activity in metastatic clear cell renal cell carcinoma (ccRCC). Data on the activity of these agents in patients with non-clear cell RCC (nccRCC) or patients with sarcomatoid/rhabdoid differentiation are limited. In this multicenter analysis, we e...

    journal_title:Cancer immunology research

    pub_type: 杂志文章,多中心研究


    authors: McKay RR,Bossé D,Xie W,Wankowicz SAM,Flaifel A,Brandao R,Lalani AA,Martini DJ,Wei XX,Braun DA,Van Allen E,Castellano D,De Velasco G,Wells JC,Heng DY,Fay AP,Schutz FA,Hsu J,Pal SK,Lee JL,Hsieh JJ,Harshman LC,Si

    更新日期:2018-07-01 00:00:00

  • Endogenous Neoantigen-Specific CD8 T Cells Identified in Two Glioblastoma Models Using a Cancer Immunogenomics Approach.

    abstract::The "cancer immunogenomics" paradigm has facilitated the search for tumor-specific antigens over the last 4 years by applying comprehensive cancer genomics to tumor antigen discovery. We applied this methodology to identify tumor-specific "neoantigens" in the C57BL/6-derived GL261 and VM/Dk-derived SMA-560 tumor model...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Johanns TM,Ward JP,Miller CA,Wilson C,Kobayashi DK,Bender D,Fu Y,Alexandrov A,Mardis ER,Artyomov MN,Schreiber RD,Dunn GP

    更新日期:2016-12-01 00:00:00

  • Insights into Tumor-Associated Tertiary Lymphoid Structures: Novel Targets for Antitumor Immunity and Cancer Immunotherapy.

    abstract::Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that phenotypically resemble conventional secondary lymphoid organs and are commonly found at sites of chronic inflammation. They are also found in a wide variety of primary and metastatic human tumors. The presence of tumor-associated TLS (TA-TLS) is ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章,评审


    authors: Rodriguez AB,Engelhard VH

    更新日期:2020-11-01 00:00:00

  • Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

    abstract::Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Chen YT,Panarelli NC,Piotti KC,Yantiss RK

    更新日期:2014-05-01 00:00:00

  • CD4 T cells require ICOS-mediated PI3K signaling to increase T-Bet expression in the setting of anti-CTLA-4 therapy.

    abstract::The transcription factor T-bet controls the Th1 genetic program in T cells for effective antitumor responses. Anti-CTLA-4 immunotherapy elicits dramatic antitumor responses in mice and in human patients; however, factors that regulate T-bet expression during an antitumor response mediated by anti-CTLA-4 remain to be e...

    journal_title:Cancer immunology research

    pub_type: 临床试验,杂志文章


    authors: Chen H,Fu T,Suh WK,Tsavachidou D,Wen S,Gao J,Ng Tang D,He Q,Sun J,Sharma P

    更新日期:2014-02-01 00:00:00

  • An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer.

    abstract::A posteriori evidence suggests that radiotherapy to a targeted tumor can elicit an immune-mediated abscopal (ab-scopus, away from the target) effect in non-targeted tumors, when combined with an anti-cytotoxic T-lymphocyte antigen-4 monoclonal (CTLA-4) antibody. Concurrent radiotherapy and ipilimumab (a human monoclon...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Golden EB,Demaria S,Schiff PB,Chachoua A,Formenti SC

    更新日期:2013-12-01 00:00:00

  • Inverse association between programmed death ligand 1 and genes in the VEGF pathway in primary clear cell renal cell carcinoma.

    abstract::Increased angiogenesis and tumor-induced immune evasion are two mechanisms by which clear cell renal cell carcinoma (ccRCC) proliferate and metastasize; however, the relationship between these pathways in human ccRCC is poorly understood. We conducted a nested case-control study using 98 archived tumor samples from pa...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Joseph RW,Parasramka M,Eckel-Passow JE,Serie D,Wu K,Jiang L,Kalari K,Thompson RH,Huu Ho T,Castle EP,Cheville J,Kwon ED,Thompson EA,Parker A

    更新日期:2013-12-01 00:00:00

  • Systemic GM-CSF Recruits Effector T Cells into the Tumor Microenvironment in Localized Prostate Cancer.

    abstract::Granulocytic-macrophage colony-stimulating factor (GM-CSF) is used as an adjuvant in cancer vaccine trials and has the potential to enhance antitumor efficacy with immunotherapy; however, its immunologic effects are not fully understood. Here, we report results from a phase I study of neoadjuvant GM-CSF in patients wi...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Wei XX,Chan S,Kwek S,Lewis J,Dao V,Zhang L,Cooperberg MR,Ryan CJ,Lin AM,Friedlander TW,Rini B,Kane C,Simko JP,Carroll PR,Small EJ,Fong L

    更新日期:2016-11-01 00:00:00

  • Urinary Bladder Cancer Tregs Suppress MMP2 and Potentially Regulate Invasiveness.

    abstract::Regulatory T cells (Treg) have long been considered one-sided suppressors of antitumor immune responses and hence associated with poor patient outcome in cancer. However, evidence is mounting of a paradoxical positive prognostic effect of Tregs on certain malignancies, including urinary bladder cancer (UBC). This disc...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Winerdal ME,Krantz D,Hartana CA,Zirakzadeh AA,Linton L,Bergman EA,Rosenblatt R,Vasko J,Alamdari F,Hansson J,Holmström B,Johansson M,Winerdal M,Marits P,Sherif A,Winqvist O

    更新日期:2018-05-01 00:00:00

  • Human NKp44+ Group 3 Innate Lymphoid Cells Associate with Tumor-Associated Tertiary Lymphoid Structures in Colorectal Cancer.

    abstract::Innate lymphoid cells (ILC) are responsible for mucosal tissue homeostasis and are involved in the progression and suppression of several types of cancer. However, the effects of ILCs on colorectal cancer are poorly understood. We characterized human ILCs in normal colon and colorectal cancer tissue, investigating the...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Ikeda A,Ogino T,Kayama H,Okuzaki D,Nishimura J,Fujino S,Miyoshi N,Takahashi H,Uemura M,Matsuda C,Yamamoto H,Takeda K,Mizushima T,Mori M,Doki Y

    更新日期:2020-06-01 00:00:00

  • Trabectedin Reveals a Strategy of Immunomodulation in Chronic Lymphocytic Leukemia.

    abstract::Chronic lymphocytic leukemia (CLL) is a B-cell neoplasia characterized by protumor immune dysregulation involving nonmalignant cells of the microenvironment, including T lymphocytes and tumor-associated myeloid cells. Although therapeutic agents have improved treatment options for CLL, many patients still fail to resp...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Banerjee P,Zhang R,Ivan C,Galletti G,Clise-Dwyer K,Barbaglio F,Scarfò L,Aracil M,Klein C,Wierda W,Plunkett W,Caligaris-Cappio F,Gandhi V,Keating MJ,Bertilaccio MTS

    更新日期:2019-12-01 00:00:00

  • Tumor Cell-Intrinsic USP22 Suppresses Antitumor Immunity in Pancreatic Cancer.

    abstract::Although immune checkpoint blockade (ICB) improves clinical outcome in several types of malignancies, pancreatic ductal adenocarcinoma (PDA) remains refractory to this therapy. Preclinical studies have demonstrated that the relative abundance of suppressive myeloid cells versus cytotoxic T cells determines the efficac...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Li J,Yuan S,Norgard RJ,Yan F,Yamazoe T,Blanco A,Stanger BZ

    更新日期:2020-03-01 00:00:00

  • Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells.

    abstract::Type I interferon (IFN-I) is a class of antiviral immunomodulatory cytokines involved in many stages of tumor initiation and progression. IFN-I acts directly on tumor cells to inhibit cell growth and indirectly by activating immune cells to mount antitumor responses. To understand the role of endogenous IFN-I in spont...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Castiello L,Sestili P,Schiavoni G,Dattilo R,Monque DM,Ciaffoni F,Iezzi M,Lamolinara A,Sistigu A,Moschella F,Pacca AM,Macchia D,Ferrantini M,Zeuner A,Biffoni M,Proietti E,Belardelli F,Aricò E

    更新日期:2018-06-01 00:00:00

  • Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable.

    abstract::Immunotherapy of immunologically cold solid tumors may require multiple agents to engage immune effector cells, expand effector populations and activities, and enable immune responses in the tumor microenvironment (TME). To target these distinct phenomena, we strategically chose five clinical-stage immuno-oncology age...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Fabian KP,Malamas AS,Padget MR,Solocinski K,Wolfson B,Fujii R,Abdul Sater H,Schlom J,Hodge JW

    更新日期:2020-12-22 00:00:00

  • Antitumor T-cell Immunity Contributes to Pancreatic Cancer Immune Resistance.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States. Pancreatic tumors are minimally infiltrated by T cells and are largely refractory to immunotherapy. Accordingly, the role of T-cell immunity in pancreatic cancer has been somewhat overlooked. Here, we hypothesized ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Ajina R,Malchiodi ZX,Fitzgerald AA,Zuo A,Wang S,Moussa M,Cooper CJ,Shen Y,Johnson QR,Parks JM,Smith JC,Catalfamo M,Fertig EJ,Jablonski SA,Weiner LM

    更新日期:2021-01-28 00:00:00

  • Microtubule-depolymerizing agents used in antibody-drug conjugates induce antitumor immunity by stimulation of dendritic cells.

    abstract::Antibody-drug conjugates (ADC) are emerging as powerful treatment strategies with outstanding target-specificity and high therapeutic activity in patients with cancer. Brentuximab vedotin represents a first-in-class ADC directed against CD30(+) malignancies. We hypothesized that its sustained clinical responses could ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Müller P,Martin K,Theurich S,Schreiner J,Savic S,Terszowski G,Lardinois D,Heinzelmann-Schwarz VA,Schlaak M,Kvasnicka HM,Spagnoli G,Dirnhofer S,Speiser DE,von Bergwelt-Baildon M,Zippelius A

    更新日期:2014-08-01 00:00:00

  • Deciphering the Immunomodulatory Capacity of Oncolytic Vaccinia Virus to Enhance the Immune Response to Breast Cancer.

    abstract::Vaccinia virus (VACV) is a double-stranded DNA virus that devotes a large portion of its 200 kbp genome to suppressing and manipulating the immune response of its host. Here, we investigated how targeted removal of immunomodulatory genes from the VACV genome impacted immune cells in the tumor microenvironment with the...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Umer BA,Noyce RS,Franczak BC,Shenouda MM,Kelly RG,Favis NA,Desaulniers M,Baldwin TA,Hitt MM,Evans DH

    更新日期:2020-05-01 00:00:00

  • Escalating regulation of 5T4-specific IFN-γ+ CD4+ T cells distinguishes colorectal cancer patients from healthy controls and provides a target for in vivo therapy.

    abstract::The relationship between the adaptive CD4+ T cell response and human cancer is unclear. The oncofetal antigen 5T4 is expressed on many human carcinomas, including colorectal cancer (CRC) cells, but has limited expression on normal tissues. We previously identified anti-5T4 CD4+ T cells in a proportion of CRC patients,...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Scurr M,Bloom A,Pembroke T,Srinivasan R,Brown C,Smart K,Bridgeman H,Davies M,Hargest R,Phillips S,Christian A,Hockey T,Gallimore A,Godkin A

    更新日期:2013-12-01 00:00:00

  • Survivorship in Immune Therapy: Assessing Chronic Immune Toxicities, Health Outcomes, and Functional Status among Long-term Ipilimumab Survivors at a Single Referral Center.

    abstract::Ipilimumab, a novel immune checkpoint inhibitor, is associated with long-term survival in approximately 20% of patients with advanced melanoma and is also being evaluated in the adjuvant setting. With this growing cohort of survivors, long-term health outcomes, chronic toxicities, and functional outcomes among survivo...

    journal_title:Cancer immunology research

    pub_type: 临床试验,杂志文章


    authors: Johnson DB,Friedman DL,Berry E,Decker I,Ye F,Zhao S,Morgans AK,Puzanov I,Sosman JA,Lovly CM

    更新日期:2015-05-01 00:00:00

  • Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab.

    abstract::We conducted in vitro studies and a clinical trial for patients with squamous cell carcinoma of the head and neck (SCCHN) to study the relationship between FcγRIIIa polymorphisms and antibody-dependent cellular cytotoxicity (ADCC). In vitro, FcγRIIIa genotype was correlated with ADCC and innate cytotoxicity using natu...

    journal_title:Cancer immunology research

    pub_type: 杂志文章,多中心研究


    authors: Taylor RJ,Saloura V,Jain A,Goloubeva O,Wong S,Kronsberg S,Nagilla M,Silpino L,de Souza J,Seiwert T,Vokes E,Villaflor V,Cohen EE

    更新日期:2015-05-01 00:00:00

  • Activated Eosinophils Exert Antitumorigenic Activities in Colorectal Cancer.

    abstract::Immunotherapies targeting T lymphocytes are revolutionizing cancer therapy but only benefit a subset of patients, especially in colorectal cancer. Thus, additional insight into the tumor microenvironment (TME) is required. Eosinophils are bone marrow-derived cells that have been largely studied in the context of aller...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Reichman H,Itan M,Rozenberg P,Yarmolovski T,Brazowski E,Varol C,Gluck N,Shapira S,Arber N,Qimron U,Karo-Atar D,Lee JJ,Munitz A

    更新日期:2019-03-01 00:00:00

  • Protective Innate Immune Variants in Racial/Ethnic Disparities of Breast and Prostate Cancer.

    abstract::Individuals of African descent are disproportionately affected by specific complex diseases, such as breast and prostate cancer, which are driven by both biological and nonbiological factors. In the case of breast cancer, there is clear evidence that psychosocial factors (environment, socioeconomic status, health beha...

    journal_title:Cancer immunology research

    pub_type: 杂志文章,评审


    authors: Yeyeodu ST,Kidd LR,Kimbro KS

    更新日期:2019-09-01 00:00:00

  • Constitutive IDO1 Expression in Human Tumors Is Driven by Cyclooxygenase-2 and Mediates Intrinsic Immune Resistance.

    abstract::Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. ...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Hennequart M,Pilotte L,Cane S,Hoffmann D,Stroobant V,Plaen E,Van den Eynde BJ

    更新日期:2017-08-01 00:00:00

  • Phenotypic and Genomic Determinants of Immunotherapy Response Associated with Squamousness.

    abstract::Advanced and metastatic squamous cell carcinomas (SCC) are common and difficult-to-treat malignancies. We assessed 75 immunotherapy-treated patients with SCC from a clinically annotated database of 2,651 patients, as well as 9,407 patients from a deidentified database for molecular features that might influence checkp...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Goodman AM,Kato S,Chattopadhyay R,Okamura R,Saunders IM,Montesion M,Frampton GM,Miller VA,Daniels GA,Kurzrock R

    更新日期:2019-06-01 00:00:00

  • NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome.

    abstract::Natural killer cell (NKc)-based therapies offer promising outcomes in patients with tumors, but they could improve with appropriate selection of donors and optimization of methods to expand NKcs in vitro Education through licensing interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) and NKG2A w...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Guillamón CF,Martínez-Sánchez MV,Gimeno L,Mrowiec A,Martínez-García J,Server-Pastor G,Martínez-Escribano J,Torroba A,Ferri B,Abellán D,Campillo JA,Legaz I,López-Álvarez MR,Moya-Quiles MR,Muro M,Minguela A

    更新日期:2018-12-01 00:00:00

  • NK Cells Expressing a Chimeric Activating Receptor Eliminate MDSCs and Rescue Impaired CAR-T Cell Activity against Solid Tumors.

    abstract::Solid tumors are refractory to cellular immunotherapies in part because they contain suppressive immune effectors such as myeloid-derived suppressor cells (MDSCs) that inhibit cytotoxic lymphocytes. Strategies to reverse the suppressive tumor microenvironment (TME) should also attract and activate immune effectors wit...

    journal_title:Cancer immunology research

    pub_type: 杂志文章


    authors: Parihar R,Rivas C,Huynh M,Omer B,Lapteva N,Metelitsa LS,Gottschalk SM,Rooney CM

    更新日期:2019-03-01 00:00:00