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What We're Reading

Cancer Immunology at the Crossroads

Cancer Immunology Miniature

  • Cancer Immunology Miniature
    Responsiveness to PD-1 Blockade in End-Stage Colon Cancer with Gene Locus 9p24.1 Copy-Number Gain
    Anne Hansen Ree, Vigdis Nygaard, Hege G. Russnes, Daniel Heinrich, Vegard Nygaard, Christin Johansen, Inger Riise Bergheim, Eivind Hovig, Klaus Beiske, Anne Negård, Anne-Lise Børresen-Dale, Kjersti Flatmark and Gunhild M. Mælandsmo
    Cancer Immunol Res May 1 2019 7 (5) 701-706; DOI:10.1158/2326-6066.CIR-18-0777

    Most patients with metastasis of large bowel cancer do not benefit from immune therapy. This case study shows that a rare gene mutation, termed 9p24.1 copy-number gain, in this otherwise incurable tumor provoked a response to immune therapy.

Research Articles

  • Research Articles | AuthorChoice
    Siglec-9 Regulates an Effector Memory CD8+ T-cell Subset That Congregates in the Melanoma Tumor Microenvironment
    Quentin Haas, Kayluz Frias Boligan, Camilla Jandus, Christoph Schneider, Cedric Simillion, Michal A. Stanczak, Monika Haubitz, Seyed Morteza Seyed Jafari, Alfred Zippelius, Gabriela M. Baerlocher, Heinz Läubli, Robert E. Hunger, Pedro Romero, Hans-Uwe Simon and Stephan von Gunten
    Cancer Immunol Res May 1 2019 7 (5) 707-718; DOI:10.1158/2326-6066.CIR-18-0505

    The lectin Siglec-9 can regulate TCR signaling and effector function of human cytotoxic CD8+ T cells. Siglec-9 expression defines a subset of effector memory CD8+ T cells that is prevalent in melanoma tissues.

  • Research Articles
    Performance Evaluation of MHC Class-I Binding Prediction Tools Based on an Experimentally Validated MHC–Peptide Binding Data Set
    Maria Bonsack, Stephanie Hoppe, Jan Winter, Diana Tichy, Christine Zeller, Marius D. Küpper, Eva C. Schitter, Renata Blatnik and Angelika B. Riemer
    Cancer Immunol Res May 1 2019 7 (5) 719-736; DOI:10.1158/2326-6066.CIR-18-0584

    Evaluation of MHC class-I binding predictors based on experimentally validated binders revealed that individual thresholds are needed for different HLA types and peptide lengths to optimize sensitivity and increase the number of epitopes as potential targets for immunotherapy.

  • Research Articles | AuthorChoice
    Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures
    Dongqiang Zeng, Meiyi Li, Rui Zhou, Jingwen Zhang, Huiying Sun, Min Shi, Jianping Bin, Yulin Liao, Jinjun Rao and Wangjun Liao
    Cancer Immunol Res May 1 2019 7 (5) 737-750; DOI:10.1158/2326-6066.CIR-18-0436

    Gastric cancer TME infiltration patterns were determined and systematically correlated with TME cell phenotypes, genomic traits, and patient clinicopathological features to establish the “TMEscore.” This score was a prognostic and predictive factor for immune checkpoint blockade response.

  • Research Articles | AuthorChoice
    Combined Low Densities of FoxP3+ and CD3+ Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression
    Tommaso Cavalleri, Paolo Bianchi, Gianluca Basso, Giuseppe Celesti, Fabio Grizzi, Paola Bossi, Luana Greco, Calogero Pitrone, Emanuele Valtorta, Gianluca Mauri, Mauro Truini, Filippo Gustavo Dall'Olio, Giovanni Brandi, Andrea Sartore-Bianchi, Luigi Ricciardiello, Valter Torri, Lorenza Rimassa, Salvatore Siena, Alberto Mantovani, Alberto Malesci and Luigi Laghi; on behalf of Alleanza contro il Cancro (ACC) Colorectal Cancer Working Group
    Cancer Immunol Res May 1 2019 7 (5) 751-758; DOI:10.1158/2326-6066.CIR-18-0661

    For nonmetastatic colorectal cancer, FoxP3+ and CD3+ T-cell densities have prognostic value up to stage III is reached. Loss of prognostic value at that point indicates that various T-cell subsets are differentially influential as the cancer progresses.

  • Research Articles
    IL15 Enhances CAR-T Cell Antitumor Activity by Reducing mTORC1 Activity and Preserving Their Stem Cell Memory Phenotype
    Darya Alizadeh, Robyn A. Wong, Xin Yang, Dongrui Wang, Joseph R. Pecoraro, Cheng-Fu Kuo, Brenda Aguilar, Yue Qi, David K. Ann, Renate Starr, Ryan Urak, Xiuli Wang, Stephen J. Forman and Christine E. Brown
    Cancer Immunol Res May 1 2019 7 (5) 759-772; DOI:10.1158/2326-6066.CIR-18-0466

    IL15 promotes metabolically fit CAR-T cells with a lessdifferentiated stem cell memory phenotype. Addition of IL15 is a clinically translatable method for improving the antitumor function of ex vivo expanded CAR-T cells, which could improve outcomes for patients.

  • Research Articles
    Cancer Immunotherapy with T Cells Carrying Bispecific Receptors That Mimic Antibodies
    Sarah Ahn, Jingjing Li, Chuang Sun, Keliang Gao, Koichi Hirabayashi, Hongxia Li, Barbara Savoldo, Rihe Liu and Gianpietro Dotti
    Cancer Immunol Res May 1 2019 7 (5) 773-783; DOI:10.1158/2326-6066.CIR-18-0636

    CAR T-cell antitumor therapy fails when the tumor loses expression of the chosen epitope. Receptors that mimic antibodies and that recognize two epitopes may reduce the chances for tumor cells to escape immune surveillance.

  • Research Articles
    A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer
    Hagma H. Workel, Joyce M. Lubbers, Roland Arnold, Thalina M. Prins, Pieter van der Vlies, Kim de Lange, Tjalling Bosse, Inge C. van Gool, Florine A. Eggink, Maartje C.A. Wouters, Fenne L. Komdeur, Elisabeth C. van der Slikke, Carien L. Creutzberg, Arjan Kol, Annechien Plat, Mark Glaire, David N. Church, Hans W. Nijman and Marco de Bruyn
    Cancer Immunol Res May 1 2019 7 (5) 784-796; DOI:10.1158/2326-6066.CIR-18-0517

    TGFβ stimulation of activated CD8+ T cells from cancer patients induces upregulation of CD103 and CXCL13, which is important for tertiary lymphoid structure formation. The data highlight a role for TGFβ in coordinating immune responses against tumors.

  • Research Articles
    T Cells Specific for an Unconventional Natural Antigen Fail to Recognize Leukemic Cells
    Margot J. Pont, Rimke Oostvogels, Cornelis A.M. van Bergen, Edith D. van der Meijden, Maria W. Honders, Sophie Bliss, Marlieke L.M. Jongsma, Henk M. Lokhorst, J.H. Frederik Falkenburg, Tuna Mutis, Marieke Griffioen and Robbert M. Spaapen
    Cancer Immunol Res May 1 2019 7 (5) 797-804; DOI:10.1158/2326-6066.CIR-18-0137

    MHC-bound peptides derived from aberrant proteins may be an immunotherapeutic target on cancer cells. However, T cells recognizing such an antigen failed to react against leukemic cells. Thus, concern is warranted for immunotherapies targeting such antigens.

  • Research Articles
    Multiple Immune-Suppressive Mechanisms in Fibrolamellar Carcinoma
    Amy K. Kim, Faiz Gani, Andrew J. Layman, Sepideh Besharati, Qingfeng Zhu, Farah Succaria, Elizabeth L. Engle, Feriyl Bhaijee, Maria B. Goggins, Nicolas J. Llosa, Timothy M. Pawlik, Mark Yarchoan, Elizabeth M. Jaffee, Howard C. Simons, Janis M. Taube and Robert A. Anders
    Cancer Immunol Res May 1 2019 7 (5) 805-812; DOI:10.1158/2326-6066.CIR-18-0499

    The expression of immune checkpoint molecules PD-1, PD-L1, B7-H3, and IDO in fibrolamellar carcinoma (FLC) is related to CD8+ T-cell density. These checkpoints are clinically targetable with inhibitors. Thus, using immune checkpoint blockade may be efficacious in FLC.

  • Research Articles | AuthorChoice
    The Pseudogene Olfr29-ps1 Promotes the Suppressive Function and Differentiation of Monocytic MDSCs
    Wencong Shang, Yunhuan Gao, Zhenzhen Tang, Yuan Zhang and Rongcun Yang
    Cancer Immunol Res May 1 2019 7 (5) 813-827; DOI:10.1158/2326-6066.CIR-18-0443

    A conserved long noncoding RNA (lncRNA), pseudogene Olfr29-ps1, was identified and shown to be induced under inflammatory conditions and in melanomas. Olfr29-ps1 can regulate the immunosuppressive function and differentiation of monocytic MDSCs both in vitro and in vivo.

  • Research Articles
    Suboptimal T-cell Therapy Drives a Tumor Cell Mutator Phenotype That Promotes Escape from First-Line Treatment
    Laura Evgin, Amanda L. Huff, Timothy Kottke, Jill Thompson, Amy M. Molan, Christopher B. Driscoll, Matthew Schuelke, Kevin G. Shim, Phonphimon Wongthida, Elizabeth J. Ilett, Karen Kaluza Smith, Reuben S. Harris, Matt Coffey, Jose S. Pulido, Hardev Pandha, Peter J. Selby, Kevin J. Harrington, Alan Melcher and Richard G. Vile
    Cancer Immunol Res May 1 2019 7 (5) 828-840; DOI:10.1158/2326-6066.CIR-18-0013

    Suboptimal antitumor immunotherapy increases genomic instability in tumor cells by inducing APOBEC3. Resulting mutations can promote tumor cell escape from co-applied therapies. Immunotherapies should be optimized early to prevent a direct enhancement of tumor cell escape.

  • Research Articles
    Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway
    Costanza Maria Cristiani, Alice Turdo, Valeria Ventura, Tiziana Apuzzo, Mariaelena Capone, Gabriele Madonna, Domenico Mallardo, Cinzia Garofalo, Emilia Dora Giovannone, Antonio M. Grimaldi, Rossana Tallerico, Emanuela Marcenaro, Silvia Pesce, Genny Del Zotto, Valter Agosti, Francesco Saverio Costanzo, Elio Gulletta, Aroldo Rizzo, Alessandro Moretta, Klas Karre, Paolo A. Ascierto, Matilde Todaro and Ennio Carbone
    Cancer Immunol Res May 1 2019 7 (5) 841-852; DOI:10.1158/2326-6066.CIR-18-0651

    CCR7+NK cells and CCL19 increased as melanoma progressed. Melanoma-derived cancer stem cells overexpressed CCR7 and were efficiently recognized and killed by NK cells. CCR7 may be a biomarker for metastatic melanoma.

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