Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • Toolbox: Coding and Computation
      • Toolbox: Signatures and Cells
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Immunology Research
Cancer Immunology Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • Toolbox: Coding and Computation
      • Toolbox: Signatures and Cells
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Research Articles

Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade

Ines Pires da Silva, Anne Gallois, Sonia Jimenez-Baranda, Shaukat Khan, Ana C. Anderson, Vijay K. Kuchroo, Iman Osman and Nina Bhardwaj
Ines Pires da Silva
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne Gallois
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sonia Jimenez-Baranda
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shaukat Khan
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ana C. Anderson
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vijay K. Kuchroo
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Iman Osman
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nina Bhardwaj
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
1Cancer Institute; 2The Ronald O. Perelman Department of Dermatology, New York University Langone Medical Center; 3Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine; 4Icahn School of Medicine at Mount Sinai, New York, New York; 5Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6Instituto Português de Oncologia de Lisboa Francisco Gentil; and 7Programme for Advanced Medical Education, Lisbon, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/2326-6066.CIR-13-0171 Published May 2014
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Additional Files
  • Figure 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1.

    Melanoma donor (MD) NK cells upregulate inhibitory receptors and downregulate activating receptors. Graphs compare the expression of the inhibitory receptors KIR3DL1 [healthy donors (HD), n = 18; melanoma donors, n = 8] and KIR2DL3 (healthy donors, n = 26; melanoma donors, n = 12) and the activating receptors NKG2D (healthy donors, n = 25; melanoma donors, n = 12), NKp46 (healthy donors, n = 20; melanoma donors, n = 11), and DNAM-1 (healthy donors, n = 10; melanoma donors, n = 10), in peripheral blood NK cells purified from healthy donors and from patients with melanoma. Right, plots depicting the expression of KIR3DL1, KIR2DL3, NKG2D, NKp46, and DNAM-1 according to CD56 expression in NK cells from a representative healthy donor and a representative melanoma patient. All experiments were performed in duplicate.

  • Figure 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2.

    Melanoma donor (MD) NK cells are functionally impaired/exhausted. A, freshly purified NK cells [healthy donors (HD), n = 12; melanoma donors, n = 5] were stimulated with 200 U/mL of IL-2. Expression of IL-2R (α-chain), IFN-γ production, and cytotoxicity (Lamp-1 expression) were monitored every 2 days over 6 days (day 0, 2, 4, and 6) by flow cytometry. B, the percentage of Lamp-1+ NK cells from healthy (n = 30) and melanoma donors (n = 12) after a cytotoxic assay is shown using K562 cells as target cells (top left). The percentage of IFN-γ+ NK cells from healthy (n = 22) and melanoma donors (n = 9) is shown after 4 hours of stimulation with IL-12 (middle left). The percentage of proliferating NK cells from healthy (n = 10) and melanoma donors (n = 7) is shown after 6 days of culture in the presence of 200 U/mL of IL-2 (bottom left). On the right panel of each graph, plots depicting the expression of Lamp-1, IFN-γ, and CFSE in NK cells purified from a representative healthy donor and a representative melanoma patient are shown. C, graphs representing the MFI of T-bet and Eomes on NK cells purified from healthy (n = 19) and melanoma donors (n = 14). Representative plots are shown (isotype control, black; healthy donors, unfilled; melanoma donors, gray). All experiments were performed in duplicate.

  • Figure 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 3.

    Tim-3 is upregulated in melanoma donor (MD) NK cells. A, graph comparing Tim-3 expression in NK cells from healthy donors [healthy donors (HD), n = 45) and patients with melanoma (melanoma donors, n = 41). Represented as the percentage of Tim-3+ cells (left) and the MFI of the Tim-3+ population (right). B, the graphs show the percentage (left) and MFI (right) of Tim-3+ NK cells from healthy donors (n = 30) and patients with melanoma stage I (n = 47), II (n = 18), and III/IV (n = 18). All experiments were performed in duplicate.

  • Figure 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 4.

    Tim-3 engagement inhibits NK-cell functions. A, the percentage of LAMP-1+ (n = 8) and B, the MFI of IFN-γ+ cells (n = 6) of NK cells from melanoma donors preincubated with IgG-coated beads or anti–Tim-3-coated beads for 2 hours before evaluating the cytotoxic function or IFN-γ production. C, reverse-ADCC assay using FcR+ P815 cells. NK cells from melanoma patients were cocultured with P815 cells and different antibodies were added to the reaction: anti–Tim-3, anti-CD94 (negative control), or anti-CD16 (positive control). Data were normalized to the values obtained for the condition: (A and B) with IgG-coated beads (100%); (C) with no antibody. All experiments were performed in duplicate.

  • Figure 5.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 5.

    NK-cell exhaustion can be reversed by Tim-3 blockade. A, graph represents the expression of LAMP-1 (n = 15; MFI) in NK cells from melanoma donors incubated with 10 or 20 μg/mL of soluble Tim-3 blocking antibody 1 hour before the cytotoxic assay. B, the percentage of CFSE+7-AAD+ K562 cells (percentage of killed K562 cells) in the presence of 10 μg/mL of two different Tim-3 blocking antibodies (clone 2E2 or R&D Systems #AF2365) 1 hour before the killing assay (n = 9 melanoma donors). Graphs represent the expression of IFN-γ (C; n = 12; MFI) and the percentage of proliferating cells (D; n = 10; %) in NK cells from melanoma donors incubated with 10 or 20 μg/mL of soluble Tim-3 blocking antibody 1 hour before the functional assays. A, C, and D, the expression of LAMP-1, IFN-γ production, and proliferation with (right) and without (middle) Tim-3 blockade from a representative melanoma patient. Data were normalized to the values obtained for the condition without blocking antibody. All experiments were performed in duplicate.

  • Figure 6.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 6.

    Soluble Tim-3 blocking antibody induces internalization of Tim-3 and upregulation of IL-2R (α- and γ-chains). A, plot depicting the decrease of Tim-3 expression in the membrane of NK cells after 1 hour of treatment with soluble Tim-3 blocking antibody. B, the graph represents the MFI of NK cells positive for the PE-conjugated, anti-mouse IgG antibody, with or without permeabilization (n = 6). C, the previous experiment was also repeated including an isotype control. The graph shows the percentage of cells positive for the PE-conjugated, anti-mouse IgG antibody after 1 hour of incubation with antibodies (n = 6). D, the graph represents the MFI of Lamp-1+ NK cells from healthy donors (n = 6) after a cytotoxic assay with K562 cells. Left, NK cells were preincubated (2 hours) with anti–Tim-3-coated beads or IgG-coated beads. Right, soluble Tim-3 blocking antibody was added 1 hour before cross-linking with anti–Tim-3-coated beads as described previously. Data were normalized to the values obtained for the condition with beads alone. E, the plots show the expression of IL-2R α- and γ-chains (percentage of positive cells) in NK cells untreated or after 1 hour of treatment with 10 μg/mL of soluble Tim-3 blocking antibody (n = 7). Data were normalized to the values obtained for the condition without blocking antibody. F, the graph depicts the percentage of Lamp-1+ NK cells after 2 days of culture with 200 U/mL of IL-2, untreated or treated with blocking antibody for α-, β-, or γ-chain (n = 5). All experiments were performed in duplicate.

Tables

  • Figures
  • Additional Files
  • Table 1.

    Tim-3 expression (percentage and MFI) according to demographic and clinical parameters with well-known prognostic value

    Demographic and clinical parametersNumber of patients[N = 83 (%)]Tim-3+ cells (%)Mean (SD)PTim-3+ cells (MFI)Mean (SD)P
    Age groups, ya0.41220.9363
     ≤4522 (27)71.77 (10.78)31.30 (5.953)
     46–7030 (36)69.51 (13.52)30.94 (6.650)
     ≥7131 (37)66.34 (18.15)30.62 (7.319)
    Genderb0.75440.4382
     Female27 (33)69.19 (12.67)30.09 (6.630)
     Male56 (67)69.28 (15.85)31.31 (6.701)
    Stagea0.21160.0114
     I47 (56)66.01 (15.78)29.07 (5.303)
     II18 (22)69.93 (17.45)32.39 (7.895)
     III/IV18 (22)73.28 (9.973)34.30 (8.479)
    Thickness, mmb0.0410.0059
     ≤147 (57)66.03 (15.47)29.18 (5.642)
     >136 (43)72.70 (13.20)33.18 (7.166)
    Mitotic indexb0.00560.0278
     <1/mm235 (42)65.01 (15.83)29.28 (5.771)
     ≥1/mm242 (51)73.54 (10.21)32.46 (6.540)
     Unclassified6 (7)
    Ulcerationb0.03510.0466
     Absent58 (70)67.51 (15.34)30.19 (6.263)
     Present19 (23)75.58 (9.979)33.61 (6.811)
     Unclassified6 (7)
    LN statusb0.32800.8242
     Negative70 (84)68.24 (15.58)30.85 (6.875)
     Positive13 (16)72.64 (9.389)31.30 (5.647)
    Metastasisb0.14760.0092
     Absent74 (89)68.10 (15.22)30.26 (6.105)
     Present9 (11)75.70 (8.996)36.31 (8.840)

    Abbreviation: LN, lymph node.

    • ↵aOne-way ANOVA.

    • ↵bUnpaired t test.

Additional Files

  • Figures
  • Tables
  • Supplementary Data

    Files in this Data Supplement:

    • Supplementary Figure Legends - PDF file - 100K
    • Supplementary Figure 1 - PDF file - 172K, Fig. S1. NK cells from melanoma patients up-regulate inhibitory receptors and down-regulate activating receptors.
    • Supplementary Figure 2 - PDF file - 93K, Fig. S2. NK cells from melanoma patients down-regulate the expression of cytokine receptors, rendering them refractory to cytokine stimulation.
    • Supplementary Figure 3 - PDF file - 72K, Fig. S3. MD NK cells are functionally impaired/exhausted.
    • Supplementary Figure 4 - PDF file - 87K, Fig. S4. Tim-3 is up-regulated in MD NK cells.
    • Supplementary Figure 5 - PDF file - 81K, Fig. S5. Tim-3 engagement on NK cells from healthy donors inhibits their cytotoxicity.
    • Supplementary Figure 6 - PDF file - 119K, Fig. S6. Tim-3 engagement by Galectin-9 on NK cells from healthy donors and melanoma patients inhibits their cytotoxicity.
    • Supplementary Figure 7 - PDF file - 234K, Fig. S7. Tim-3 blockade improves NK cell function.
    • Supplementary Figure 8 - PDF file - 59K, Fig. S8. Tim-3 blockade has no effect in NK cell viability but increases the expression of CD16 in these cells.
PreviousNext
Back to top
Cancer Immunology Research: 2 (5)
May 2014
Volume 2, Issue 5
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Immunology Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade
(Your Name) has forwarded a page to you from Cancer Immunology Research
(Your Name) thought you would be interested in this article in Cancer Immunology Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade
Ines Pires da Silva, Anne Gallois, Sonia Jimenez-Baranda, Shaukat Khan, Ana C. Anderson, Vijay K. Kuchroo, Iman Osman and Nina Bhardwaj
Cancer Immunol Res May 1 2014 (2) (5) 410-422; DOI: 10.1158/2326-6066.CIR-13-0171

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade
Ines Pires da Silva, Anne Gallois, Sonia Jimenez-Baranda, Shaukat Khan, Ana C. Anderson, Vijay K. Kuchroo, Iman Osman and Nina Bhardwaj
Cancer Immunol Res May 1 2014 (2) (5) 410-422; DOI: 10.1158/2326-6066.CIR-13-0171
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Grant Support
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Nutlin-3a: An Immune-Checkpoint Activator for NK Cells in Neuroblastoma
  • Therapy to Engage, Expand, and Enable Antitumor Responses
  • Dietary Fructose Promotes Resistance to Cancer Immunotherapy
Show more Research Articles
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Cancer Immunology Essentials

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Immunology Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Immunology Research
eISSN: 2326-6074
ISSN: 2326-6066

Advertisement