Dendritic Cells in Shaping Anti-Tumor T Cell Response

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Jun 27

PMID 38927916

Authors

Luciano Mazzoccoli

Bei Liu

Affiliations

Soon will be listed here.

Abstract

Among professional antigen-presenting cells, dendritic cells (DCs) orchestrate innate and adaptive immunity and play a pivotal role in anti-tumor immunity. DCs are a heterogeneous population with varying functions in the tumor microenvironment (TME). Tumor-associated DCs differentiate developmentally and functionally into three main subsets: conventional DCs (cDCs), plasmacytoid DCs (pDCs), and monocyte-derived DCs (MoDCs). There are two major subsets of cDCs in TME, cDC1 and cDC2. cDC1 is critical for cross-presenting tumor antigens to activate cytotoxic CD8 T cells and is also required for priming earlier CD4 T cells in certain solid tumors. cDC2 is vital for priming anti-tumor CD4 T cells in multiple tumor models. pDC is a unique subset of DCs and produces type I IFN through TLR7 and TLR9. Studies have shown that pDCs are related to immunosuppression in the TME through the secretion of immunosuppressive cytokines and by promoting regulatory T cells. MoDCs differentiate separately from monocytes in response to inflammatory cues and infection. Also, MoDCs can cross-prime CD8 T cells. In this review, we summarize the subsets and functions of DCs. We also discuss the role of different DC subsets in shaping T cell immunity in TME and targeting DCs for potential immunotherapeutic benefits against cancer.

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References

Ghirelli C, Reyal F, Jeanmougin M, Zollinger R, Sirven P, Michea P . Breast Cancer Cell-Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes. Cancer Res. 2015; 75(14):2775-87. DOI: 10.1158/0008-5472.CAN-14-2386. View

Bottcher J, Reis e Sousa C . The Role of Type 1 Conventional Dendritic Cells in Cancer Immunity. Trends Cancer. 2018; 4(11):784-792. PMC: 6207145. DOI: 10.1016/j.trecan.2018.09.001. View

Kvedaraite E, Ginhoux F . Human dendritic cells in cancer. Sci Immunol. 2022; 7(70):eabm9409. DOI: 10.1126/sciimmunol.abm9409. View

Spranger S, Dai D, Horton B, Gajewski T . Tumor-Residing Batf3 Dendritic Cells Are Required for Effector T Cell Trafficking and Adoptive T Cell Therapy. Cancer Cell. 2017; 31(5):711-723.e4. PMC: 5650691. DOI: 10.1016/j.ccell.2017.04.003. View

Tarhini A, Cherian J, Moschos S, Tawbi H, Shuai Y, Gooding W . Safety and efficacy of combination immunotherapy with interferon alfa-2b and tremelimumab in patients with stage IV melanoma. J Clin Oncol. 2011; 30(3):322-8. PMC: 3422533. DOI: 10.1200/JCO.2011.37.5394. View

Ueno H, Klechevsky E, Schmitt N, Ni L, Flamar A, Zurawski S . Targeting human dendritic cell subsets for improved vaccines. Semin Immunol. 2011; 23(1):21-7. PMC: 3071344. DOI: 10.1016/j.smim.2011.01.004. View

Gardner A, Ruffell B . Dendritic Cells and Cancer Immunity. Trends Immunol. 2016; 37(12):855-865. PMC: 5135568. DOI: 10.1016/j.it.2016.09.006. View

Aspord C, Leccia M, Charles J, Plumas J . Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL. Cancer Immunol Res. 2014; 1(6):402-15. DOI: 10.1158/2326-6066.CIR-13-0114-T. View

Cubillos-Ruiz J, Baird J, Tesone A, Rutkowski M, Scarlett U, Camposeco-Jacobs A . Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer. Cancer Res. 2012; 72(7):1683-93. PMC: 3319850. DOI: 10.1158/0008-5472.CAN-11-3160. View

10.

Laheurte C, Seffar E, Gravelin E, Lecuelle J, Renaudin A, Boullerot L . Interplay between plasmacytoid dendritic cells and tumor-specific T cells in peripheral blood influences long-term survival in non-small cell lung carcinoma. Cancer Immunol Immunother. 2022; 72(3):579-589. PMC: 10992197. DOI: 10.1007/s00262-022-03271-9. View

11.

Longaray J, Dias C, Scholl J, Battastini A, Figueiro F . Investigation of co-treatment multi-targeting approaches in breast cancer cell lines. Eur J Pharmacol. 2024; 966:176328. DOI: 10.1016/j.ejphar.2024.176328. View

12.

Segura E, Amigorena S . Cross-Presentation in Mouse and Human Dendritic Cells. Adv Immunol. 2015; 127:1-31. DOI: 10.1016/bs.ai.2015.03.002. View

13.

Subtil B, van der Hoorn I, Cuenca-Escalona J, Becker A, Alvarez-Begue M, Iyer K . cDC2 plasticity and acquisition of a DC3-like phenotype mediated by IL-6 and PGE2 in a patient-derived colorectal cancer organoids model. Eur J Immunol. 2024; 54(6):e2350891. DOI: 10.1002/eji.202350891. View

14.

Persson E, Uronen-Hansson H, Semmrich M, Rivollier A, Hagerbrand K, Marsal J . IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation. Immunity. 2013; 38(5):958-69. DOI: 10.1016/j.immuni.2013.03.009. View

15.

Dutertre C, Becht E, Irac S, Khalilnezhad A, Narang V, Khalilnezhad S . Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells. Immunity. 2019; 51(3):573-589.e8. DOI: 10.1016/j.immuni.2019.08.008. View

16.

Steinman R, Hawiger D, Nussenzweig M . Tolerogenic dendritic cells. Annu Rev Immunol. 2003; 21:685-711. DOI: 10.1146/annurev.immunol.21.120601.141040. View

17.

Peng W, Zhou X, Yan W, Li Y, Du C, Wang X . Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing. Oncoimmunology. 2022; 11(1):2026583. PMC: 8794254. DOI: 10.1080/2162402X.2022.2026583. View

18.

Shi W, Li X, Porter J, Ostrodi D, Yang B, Li J . Level of plasmacytoid dendritic cells is increased in non-small cell lung carcinoma. Tumour Biol. 2013; 35(3):2247-52. DOI: 10.1007/s13277-013-1297-7. View

19.

Zhang L, Conejo-Garcia J, Katsaros D, Gimotty P, Massobrio M, Regnani G . Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003; 348(3):203-13. DOI: 10.1056/NEJMoa020177. View

20.

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. PMC: 3853342. DOI: 10.1146/annurev-immunol-020711-074950. View