Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Intratumoral dendritic cells in the anti-tumor immune response

Cellular & Molecular Immunology volume 12, pages 387–390 (2015)Cite this article

Immunotherapy has become a popular approach to the treatment of cancer and is well known in the clinical management of cancer because of the exciting recent results from immunotherapy targeting the costimulatory blockade.1 Another hot topic in this field is the combination of cancer immunotherapy and chemotherapy, and interestingly, T-cell immune response to the immunogenic cell death (ICD) induced by chemotherapeutic drugs is important to the therapeutic efficacy of certain types of chemotherapy. Therefore, the questions arising are what are the initiator and activator of the anti-tumor immune response in a tumor-bearing host receiving chemotherapy or combination therapy? Is there any possibility that effective antigen-presenting cells (APCs) exist in the immunosuppressive tumor microenvironment that process the tumor antigens released from the ICD of tumor cells and then initiate a tumor-specific T-cell response? Currently, it is well accepted that the tumor microenvironment, which consists of tumor cells, tumor-associated fibroblasts, vascular endothelial cells and immunosuppressive (or at least functionally impaired) immune cells, such as myeloid-derived suppressor cells, tumor-associated macrophages (TAMs), regulatory T cells and regulatory dendritic cells (DCs),2 is immunosuppressive and tumor-promoting. Thus, the current cancer immunotherapies mainly aim to reverse this tumor immunosuppression as well as trigger an effective anti-tumor immune response, enhancing the cytotoxic ability of T cells to reject tumors.3 Therefore, further identification of the immune cell types in the tumor microenvironment, with immune-tolerating or immune-activating potential, will provide new opportunities for the design of cancer immunotherapeutics. More recently, intratumoral CD103+ DCs have been identified as active APCs in the tumor microenvironment that process antigens and are crucial to the induction of an anti-tumoral T-cell response,4,5 thus challenging the concept that immune cells are all immunosuppressive or functionally impaired in the tumor microenvironment. These new findings will inspire immunologists to rethink the interactions between the host immune system and tumors and develop new approaches to cancer immunotherapy.

In the last few decades, the tumor microenvironment has been shown to be capable of inactivating various components of the immune system responsible for tumor clearance.6 This microenvironment becomes even more intricate and variable due to the tumor-promoting polarization of immune cell differentiation and function. For example, macrophages in tumors can enhance tumor cell proliferation, invasion and metastasis; stimulate angiogenesis; and inhibit T cell-mediated anti-tumor immune responses, thus promoting tumor progression.7 Although much work has been done to identify the molecular and cellular mechanisms underlying the anti-tumor immune response and immunosuppression in the tumor microenvironment, there are still some questions that remain to be investigated. For example, why do the APCs within tumors typically fail to maintain the cytotoxic T cell (CTL) function of killing the tumor? Are there any strongly stimulatory APCs within the tumor microenvironment to induce an anti-tumor immune response? To address these concerns, immunologists have been investigating the cell types and functions of APCs in the tumor microenvironment. As the most potent professional APCs, DCs have a superior ability to activate naive T cells and play a pivotal role in the induction and maintenance of anti-tumor responses.8 The stimulatory versus inhibitory function of DCs depends on their cell subset and maturation status. Regulatory DCs in the tumor microenvironment and systemic organs have been identified to mediate suppression of T-cell responses against tumors.9,10 By contrast, marginating DCs of the tumor microenvironment can cross-present tumor antigens and stably engage tumor-specific T cells.11 Expression of the neonatal Fc receptor in DCs can mediate protective immunity against colorectal cancer.12 Moreover, DCs in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and promote a protective immune response mediated by T cells against cancer.13 Therefore, DCs represent a special population of cells that display different phenotypes and activities at the tumor site as well as exhibit differential pro-tumorigenic and anti-tumorigenic functions.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Rook AH, Raphael BA . Progress in immunotherapy of cancer. N Engl J Med 2012; 367: 1168.

    Article  CAS  PubMed  Google Scholar 

  2. Junttila MR, de Sauvage FJ . Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 2013; 501: 346–354.

    Article  CAS  PubMed  Google Scholar 

  3. Ledford H . Cancer treatment: The killer within. Nature 2014; 508: 24–26.

    Article  CAS  PubMed  Google Scholar 

  4. Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell 2014; 26: 638–652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ruffell B, Chang-Strachan D, Chan V, Rosenbusch A, Ho C, Pryer N et al. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell 2014; 26: 623–637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Marabelle A, Kohrt H, Caux C, Levy R . Intratumoral immunization: a new paradigm for cancer therapy. Clin Cancer Res 2014; 20: 1747–1756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Liu Y, Cao X . The origin and function of tumor-associated macrophages. Cell Mol Immunol 2014; doi: 10.1038/cmi.2014.83.

    Article  CAS  Google Scholar 

  8. Merad M, Sathe P, Helft J, Miller J, Mortha A . The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 2013; 31: 563–604.

    Article  CAS  PubMed  Google Scholar 

  9. Liu Q, Zhang C, Sun A, Zheng Y, Wang L, Cao X . Tumor-educated CD11bhighIalow regulatory dendritic cells suppress T cell response through arginase I. J Immunol 2009; 182: 6207–6216.

    Article  CAS  PubMed  Google Scholar 

  10. Han Y, Chen Z, Yang Y, Jiang Z, Gu Y, Liu Y et al. Human CD14+ CTLA-4+ regulatory dendritic cells suppress T-cell response by cytotoxic T-lymphocyte antigen-4-dependent IL-10 and indoleamine-2,3-dioxygenase production in hepatocellular carcinoma. Hepatology 2014; 59: 567–579.

    Article  CAS  PubMed  Google Scholar 

  11. Engelhardt JJ, Boldajipour B, Beemiller P, Pandurangi P, Sorensen C, Werb Z et al. Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. Cancer Cell 2012; 21: 402–417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Baker K, Rath T, Flak MB, Arthur JC, Chen Z, Glickman JN et al. Neonatal Fc receptor expression in dendritic cells mediates protective immunity against colorectal cancer. Immunity 2013; 39: 1095–1107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Goc J, Germain C, Vo-Bourgais TK, Lupo A, Klein C, Knockaert S et al. Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer Res 2014; 74: 705–715.

    Article  CAS  PubMed  Google Scholar 

  14. Kroemer G, Galluzzi L, Kepp O, Zitvogel L . Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013; 31: 51–72.

    Article  CAS  PubMed  Google Scholar 

  15. Fang H, Ang B, Xu X, Huang X, Wu Y, Sun Y et al. TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells. Cell Mol Immunol 2014; 11: 150–159.

    Article  CAS  PubMed  Google Scholar 

  16. Xu H, Cao X . Dendritic cell vaccines in cancer immunotherapy: from biology to translational medicine. Front Med 2011; 5: 323–332.

    Article  PubMed  Google Scholar 

  17. Quail DF, Joyce JA . Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19: 1423–1437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. McNutt M . Cancer immunotherapy. Science 2013; 342: 1417.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Key Laboratory of Medical Molecular Biology & Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences,

    Yang Liu & Xuetao Cao

  2. Department of Immunology, Peking Union Medical College, Beijing, China

    Yang Liu & Xuetao Cao

  3. National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai, China

    Xuetao Cao

Authors
  1. Yang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xuetao Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xuetao Cao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Cao, X. Intratumoral dendritic cells in the anti-tumor immune response. Cell Mol Immunol 12, 387–390 (2015). https://doi.org/10.1038/cmi.2014.130

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2014.130

This article is cited by

Search

Advanced search

Quick links