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Cancer Immunology at the Crossroads

Cancer Immunology Miniature

  • Cancer Immunology Miniature
    Clinical Significance of Pancreatic Atrophy Induced by Immune-Checkpoint Inhibitors: A Case–Control Study
    Yael Eshet, Erez Nissim Baruch, Ronnie Shapira-Frommer, Yael Steinberg-Silman, Teodor Kuznetsov, Guy Ben-Betzalel, Sameh Daher, Iris Gluck, Nethanel Asher, Sara Apter, Jacob Schachter, Jair Bar, Ben Boursi and Gal Markel
    Cancer Immunol Res December 1 2018 6 (12) 1453-1458; DOI:10.1158/2326-6066.CIR-17-0659

    Immunotherapy-induced diarrhea is usually attributed to inflammatory colitis. However, late-onset diarrhea in patients treated with PD-1 inhibitors may be caused by pancreatic atrophy, leading to exocrine insufficiency. Although steroid-resistant, this condition may be treated with oral enzyme supplements.

Research Articles

  • Research Articles
    Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma
    Fei Zhao, Kathy Evans, Christine Xiao, Nicholas DeVito, Balamayooran Theivanthiran, Alisha Holtzhausen, Peter J. Siska, Gerard C. Blobe and Brent A. Hanks
    Cancer Immunol Res December 1 2018 6 (12) 1459-1471; DOI:10.1158/2326-6066.CIR-18-0086

    Melanoma-associated fibroblasts contributed to checkpoint blockade resistance via MMP-9–dependent PD-L1 cleavage and influenced the impact of TGFβ inhibition on responses to anti–PD-1. These findings highlight the importance of understanding immunotherapy effects on the tumor microenvironment.

  • Research Articles | AuthorChoice
    FAP Delineates Heterogeneous and Functionally Divergent Stromal Cells in Immune-Excluded Breast Tumors
    Viviana Cremasco, Jillian L. Astarita, Angelo L. Grauel, Shilpa Keerthivasan, Kenzie MacIsaac, Matthew C. Woodruff, Michael Wu, Lotte Spel, Stephen Santoro, Zohreh Amoozgar, Tyler Laszewski, Sara Cruz Migoni, Konstantin Knoblich, Anne L. Fletcher, Martin LaFleur, Kai W. Wucherpfennig, Ellen Pure, Glenn Dranoff, Michael C. Carroll and Shannon J. Turley
    Cancer Immunol Res December 1 2018 6 (12) 1472-1485; DOI:10.1158/2326-6066.CIR-18-0098

    Cancer-associated stromal cells restrain responses to immunotherapy and are associated with poor prognosis. Isolation of mesenchymal cells from fresh breast tumor samples revealed subsets with distinct phenotype and immunoregulatory potential. These observations may lead to better designed immunotherapies.

  • Research Articles | AuthorChoice
    Phage-Based Anti-HER2 Vaccination Can Circumvent Immune Tolerance against Breast Cancer
    Caterina Bartolacci, Cristina Andreani, Claudia Curcio, Sergio Occhipinti, Luca Massaccesi, Mirella Giovarelli, Roberta Galeazzi, Manuela Iezzi, Martina Tilio, Valentina Gambini, Junbiao Wang, Cristina Marchini and Augusto Amici
    Cancer Immunol Res December 1 2018 6 (12) 1486-1498; DOI:10.1158/2326-6066.CIR-18-0179

    Structural and immunogenic differences between HER2 and Δ16HER2 were determined, and DNA and phage-based vaccines were developed. This vaccine strategy led to breaking immune tolerance in a breast cancer model, allowing for improved antitumor responses.

  • Research Articles | AuthorChoice
    A High-Throughput Immune-Oncology Screen Identifies EGFR Inhibitors as Potent Enhancers of Antigen-Specific Cytotoxic T-lymphocyte Tumor Cell Killing
    Patrick H. Lizotte, Ruey-Long Hong, Troy A. Luster, Megan E. Cavanaugh, Luke J. Taus, Stephen Wang, Abha Dhaneshwar, Naomi Mayman, Aaron Yang, Meghana Kulkarni, Lauren Badalucco, Erica Fitzpatrick, Hsiang-Fong Kao, Mari Kuraguchi, Mark Bittinger, Paul T. Kirschmeier, Nathanael S. Gray, David A. Barbie and Pasi A. Jänne
    Cancer Immunol Res December 1 2018 6 (12) 1511-1523; DOI:10.1158/2326-6066.CIR-18-0193

    A screening tool capable of high-throughput identification of compounds and genes affecting antitumor responses is presented. Specific EGFR inhibitors were identified and validated as enhancing T cell–mediated killing of tumor cells, providing a proof-of-principle for this approach.

  • Research Articles
    Altered Binding of Tumor Antigenic Peptides to MHC Class I Affects CD8+ T Cell–Effector Responses
    Eleanor Clancy-Thompson, Christine A. Devlin, Paul M. Tyler, Mariah M. Servos, Lestat R. Ali, Katherine S. Ventre, M. Aladdin Bhuiyan, Patrick T. Bruck, Michael E. Birnbaum and Stephanie K. Dougan
    Cancer Immunol Res December 1 2018 6 (12) 1524-1536; DOI:10.1158/2326-6066.CIR-18-0348

    Influence of T-cell priming on effector antitumor responses was evaluated. Loss of secondary contacts between a peptide non-anchor residue and MHC skews effector functions to favor cytotoxicity over cytokine production in T cells specific for a melanoma self-antigen.

  • Research Articles
    NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome
    Concepción F. Guillamón, María V. Martínez-Sánchez, Lourdes Gimeno, Anna Mrowiec, Jerónimo Martínez-García, Gerardo Server-Pastor, Jorge Martínez-Escribano, Amparo Torroba, Belén Ferri, Daniel Abellán, José A. Campillo, Isabel Legaz, María R. López-Álvarez, María Rosa Moya-Quiles, Manuel Muro and Alfredo Minguela
    Cancer Immunol Res December 1 2018 6 (12) 1537-1547; DOI:10.1158/2326-6066.CIR-18-0022

    Solid tumors modulate the expression of molecules induced by licensing interactions during NK-cell education and alter their function. Expression of these molecules can predict patient survival and have implications in the design of NK cell-based therapies.

  • Research Articles
    PD-L1 Mediates Dysfunction in Activated PD-1+ NK Cells in Head and Neck Cancer Patients
    Fernando Concha-Benavente, Benjamin Kansy, Jessica Moskovitz, Jennifer Moy, Uma Chandran and Robert L. Ferris
    Cancer Immunol Res December 1 2018 6 (12) 1548-1560; DOI:10.1158/2326-6066.CIR-18-0062

    PD-1 expression and function were assessed in NK cells from patients with head and neck cancer. NK cell dysfunction was reversed by PD-1 blockade and improved responses to cetuximab therapy, thus, providing an approach to reverse tumor immune evasion.

  • Research Articles
    Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs
    Brian J. Christmas, Christine I. Rafie, Alexander C. Hopkins, Blake A. Scott, Hayley S. Ma, Kayla A. Cruz, Skylar Woolman, Todd D. Armstrong, Roisin M. Connolly, Nilo A. Azad, Elizabeth M. Jaffee and Evanthia T. Roussos Torres
    Cancer Immunol Res December 1 2018 6 (12) 1561-1577; DOI:10.1158/2326-6066.CIR-18-0070

    The HDAC inhibitor, entiniostat, impairs myeloid immunosuppressive function, and in combination with immune checkpoint inhibitors, improves T-cell responses in models of breast and pancreatic cancers. These data provide rationale for combination therapy in patients to improve antitumor responses.

  • Research Articles | AuthorChoice
    Exosomes Released from Tumor-Associated Macrophages Transfer miRNAs That Induce a Treg/Th17 Cell Imbalance in Epithelial Ovarian Cancer
    Jieru Zhou, Xiaoduan Li, Xiaoli Wu, Ting Zhang, Qinyi Zhu, Xinjing Wang, Husheng Wang, Kai Wang, Yingying Lin and Xipeng Wang
    Cancer Immunol Res December 1 2018 6 (12) 1578-1592; DOI:10.1158/2326-6066.CIR-17-0479

    The Treg/Th17 ratio is altered in epithelial ovarian cancer. Exosomal miRNAs from tumor-associated macrophages contribute to this T-cell imbalance, which promotes an immune suppressive tumor microenvironment and favors progression and metastasis of epithelial ovarian cancer cells.

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