Tumor-Residing Batf3 Dendritic Cells Are Required for Effector T Cell Trafficking and Adoptive T Cell Therapy

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2017 May 10

PMID 28486109

Citations 724

Authors

Stefani Spranger

Daisy Dai

Brendan Horton

Thomas F Gajewski

Affiliations

Soon will be listed here.

Abstract

Effector T cells have the capability of recognizing and killing cancer cells. However, whether tumors can become immune resistant through exclusion of effector T cells from the tumor microenvironment is not known. By using a tumor model resembling non-T cell-inflamed human tumors, we assessed whether adoptive T cell transfer might overcome failed spontaneous priming. Flow cytometric assays combined with intra-vital imaging indicated failed trafficking of effector T cells into tumors. Mechanistically, this was due to the absence of CXCL9/10, which we found to be produced by CD103 dendritic cells (DCs) in T cell-inflamed tumors. Our data indicate that lack of CD103 DCs within the tumor microenvironment dominantly resists the effector phase of an anti-tumor T cell response, contributing to immune escape.

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References

Brahmer J, Tykodi S, Chow L, Hwu W, Topalian S, Hwu P . Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012; 366(26):2455-65. PMC: 3563263. DOI: 10.1056/NEJMoa1200694. View

Hodi F, ODay S, Mcdermott D, Weber R, Sosman J, Haanen J . Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363(8):711-23. PMC: 3549297. DOI: 10.1056/NEJMoa1003466. View

Bottcher J, Beyer M, Meissner F, Abdullah Z, Sander J, Hochst B . Functional classification of memory CD8(+) T cells by CX3CR1 expression. Nat Commun. 2015; 6:8306. PMC: 4667439. DOI: 10.1038/ncomms9306. View

Klebanoff C, Gattinoni L, Restifo N . CD8+ T-cell memory in tumor immunology and immunotherapy. Immunol Rev. 2006; 211:214-24. PMC: 1501075. DOI: 10.1111/j.0105-2896.2006.00391.x. View

Meijering E, Dzyubachyk O, Smal I . Methods for cell and particle tracking. Methods Enzymol. 2012; 504:183-200. DOI: 10.1016/B978-0-12-391857-4.00009-4. View

Bosenberg M, Muthusamy V, Curley D, Wang Z, Hobbs C, Nelson B . Characterization of melanocyte-specific inducible Cre recombinase transgenic mice. Genesis. 2006; 44(5):262-7. DOI: 10.1002/dvg.20205. View

Groom J, Luster A . CXCR3 in T cell function. Exp Cell Res. 2011; 317(5):620-31. PMC: 3065205. DOI: 10.1016/j.yexcr.2010.12.017. View

Mikucki M, Fisher D, Matsuzaki J, Skitzki J, Gaulin N, Muhitch J . Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints. Nat Commun. 2015; 6:7458. PMC: 4605273. DOI: 10.1038/ncomms8458. View

Joshi N, Akama-Garren E, Lu Y, Lee D, Chang G, Li A . Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses. Immunity. 2015; 43(3):579-90. PMC: 4826619. DOI: 10.1016/j.immuni.2015.08.006. View

10.

Ishikawa H, Barber G . STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature. 2008; 455(7213):674-8. PMC: 2804933. DOI: 10.1038/nature07317. View

11.

Dudley M, Wunderlich J, Robbins P, Yang J, Hwu P, Schwartzentruber D . Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002; 298(5594):850-4. PMC: 1764179. DOI: 10.1126/science.1076514. View

12.

Topalian S, Taube J, Anders R, Pardoll D . Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016; 16(5):275-87. PMC: 5381938. DOI: 10.1038/nrc.2016.36. View

13.

Edelson B, Kc W, Juang R, Kohyama M, Benoit L, Klekotka P . Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells. J Exp Med. 2010; 207(4):823-36. PMC: 2856032. DOI: 10.1084/jem.20091627. View

14.

Schietinger A, Arina A, Liu R, Wells S, Huang J, Engels B . Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer. Oncoimmunology. 2014; 2(11):e26677. PMC: 3895414. DOI: 10.4161/onci.26677. View

15.

Alexandre Y, Ghilas S, Sanchez C, Le Bon A, Crozat K, Dalod M . XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses. J Exp Med. 2015; 213(1):75-92. PMC: 4710197. DOI: 10.1084/jem.20142350. View

16.

Padovan E, Spagnoli G, Ferrantini M, Heberer M . IFN-alpha2a induces IP-10/CXCL10 and MIG/CXCL9 production in monocyte-derived dendritic cells and enhances their capacity to attract and stimulate CD8+ effector T cells. J Leukoc Biol. 2002; 71(4):669-76. View

17.

Mempel T, Henrickson S, von Andrian U . T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature. 2004; 427(6970):154-9. DOI: 10.1038/nature02238. View

18.

Matsushita H, Vesely M, Koboldt D, Rickert C, Uppaluri R, Magrini V . Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature. 2012; 482(7385):400-4. PMC: 3874809. DOI: 10.1038/nature10755. View

19.

Harlin H, Meng Y, Peterson A, Zha Y, Tretiakova M, Slingluff C . Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res. 2009; 69(7):3077-85. PMC: 3886718. DOI: 10.1158/0008-5472.CAN-08-2281. View

20.

Roberts E, Broz M, Binnewies M, Headley M, Nelson A, Wolf D . Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma. Cancer Cell. 2016; 30(2):324-336. PMC: 5374862. DOI: 10.1016/j.ccell.2016.06.003. View