. 2021 Oct 12;54(10):2338-2353.e6.

doi: 10.1016/j.immuni.2021.08.026. Epub 2021 Sep 16.

Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1⁺ CD8⁺ T cells in tumor-draining lymph nodes

Jason M Schenkel¹, Rebecca H Herbst², David Canner³, Amy Li⁴, Michelle Hillman⁵, Sean-Luc Shanahan⁵, Grace Gibbons⁵, Olivia C Smith⁵, Jonathan Y Kim⁵, Peter Westcott⁵, William L Hwang⁶, William A Freed-Pastor⁷, George Eng⁸, Michael S Cuoco⁹, Patricia Rogers⁹, Jin K Park¹⁰, Megan L Burger⁵, Orit Rozenblatt-Rosen⁹, Le Cong¹¹, Kristen E Pauken¹², Aviv Regev¹³, Tyler Jacks¹⁴

Affiliations

¹ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
² Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.
³ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
⁴ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
⁵ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA.
⁶ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Department of Radiation Oncology, Massachusetts General Hospital, Boston MA 02114.
⁷ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁹ Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.
¹⁰ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
¹¹ Departments of Pathology, Stanford University, Stanford, CA 94305, USA.
¹² Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
¹³ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: aviv.regev.sc@gmail.com.
¹⁴ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: tjacks@mit.edu.

PMID: 34534439
PMCID: PMC8604155
DOI: 10.1016/j.immuni.2021.08.026

Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1⁺ CD8⁺ T cells in tumor-draining lymph nodes

Jason M Schenkel et al. Immunity. 2021.

. 2021 Oct 12;54(10):2338-2353.e6.

doi: 10.1016/j.immuni.2021.08.026. Epub 2021 Sep 16.

Authors

Affiliations

¹ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
² Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.
³ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
⁴ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
⁵ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA.
⁶ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Department of Radiation Oncology, Massachusetts General Hospital, Boston MA 02114.
⁷ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁸ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁹ Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA.
¹⁰ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
¹¹ Departments of Pathology, Stanford University, Stanford, CA 94305, USA.
¹² Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
¹³ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: aviv.regev.sc@gmail.com.
¹⁴ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: tjacks@mit.edu.

PMID: 34534439
PMCID: PMC8604155
DOI: 10.1016/j.immuni.2021.08.026

Abstract

In tumors, a subset of CD8⁺ T cells expressing the transcription factor TCF-1 drives the response to immune checkpoint blockade. We examined the mechanisms that maintain these cells in an autochthonous model of lung adenocarcinoma. Longitudinal sampling and single-cell sequencing of tumor-antigen specific TCF-1⁺ CD8⁺ T cells revealed that while intratumoral TCF-1⁺ CD8⁺ T cells acquired dysfunctional features and decreased in number as tumors progressed, TCF-1⁺ CD8⁺ T cell frequency in the tumor draining LN (dLN) remained stable. Two discrete intratumoral TCF-1⁺ CD8⁺ T cell subsets developed over time-a proliferative SlamF6⁺ subset and a non-cycling SlamF6^- subset. Blocking dLN egress decreased the frequency of intratumoral SlamF6⁺ TCF-1⁺ CD8⁺ T cells. Conventional type I dendritic cell (cDC1) in dLN decreased in number with tumor progression, and Flt3L+anti-CD40 treatment recovered SlamF6⁺ T cell frequencies and decreased tumor burden. Thus, cDC1s in tumor dLN maintain a reservoir of TCF-1⁺ CD8⁺ T cells and their decrease contributes to failed anti-tumor immunity.

Keywords: CD8 T cells; Flt3L; T cell dysfunction; TCF-1+; anti-CD40; migratory cDC1; single-cell RNA-seq; tumor immunology; tumor-draining lymph node.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests T.J. is a member of the Board of Directors of Amgen and Thermo Fisher Scientific. He is also a co-founder of Dragonfly Therapeutics and T2 Biosystems. T.J. serves on the Scientific Advisory Board of Dragonfly Therapeutics, SQZ Biotech, and Skyhawk Therapeutics. He is the President of Break Through Cancer. None of these affiliations represent a conflict of interest with respect to the design or execution of this study or interpretation of data presented in this manuscript. T.J. laboratory currently also receives funding from the Johnson & Johnson Lung Cancer Initiative and The Lustgarten Foundation for Pancreatic Cancer Research, but this funding did not support the research described in this manuscript. A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov until July 31, 2020. From August 1, 2020, A.R. is an employee of Genentech.

Figures

**Figure 1.. Tumor-specific CD8⁺ T cells become dysfunctional during progression of lung adenocarcinoma**
(A) Experimental schematic. Leukocytes were isolated from lungs. (B) Tumor-specific CD8⁺ T cells infiltrated tumors. Representative H-2K^b/SIINFEKL tetramer staining by flow cytometry (left, gated on CD8⁺ T cells) and by immunofluorescence microscopy (right). (C) Percent (left) and number (right) of tumor specific CD8⁺ T cells of total CD8⁺ T cells throughout KP tumor development. (D-E) tumor specific CD8⁺ T cells upregulated number (D) and level (E) of IR expression over time. (D) Percent of tumor-specific CD8⁺ T cells expressing combinations (indicated by color) of IR by flow cytometry (TIM-3, TIGIT, PD-1, LAG-3, 2B4). (E) IR geometric MFI at 5 and 16 weeks on tumor specific CD8⁺ T cells from 1 experiment, representative of 2 experiments (dot: one mouse), Mann-Whitney test. (F) Percent Ki-67⁺ of tumor specific CD8⁺ T cells at indicated weeks. (G)Ratio of IFNγ⁺ TNFα⁺ to H-2K^b/SIINFEKL tetramer⁺ of CD8⁺ T cells after *in-vitro* peptide stimulation. *p<0.05, **p<0.01, ***p<0.001, ns=not significant (p>0.05). Tukey’s multiple comparisons test unless otherwise noted. See also Supplemental Figure 1.

**Figure 2.. Single cell RNA-seq highlights distinct effector and dysfunction programs that arise during tumor progression in tumor-specific CD8⁺ T cells**
Data showing results for plate-based scRNA-seq data. (A) UMAP embedding of all CD8⁺ T cells colored by tetramer binding. (B&C) UMAP embedding of all CD8+ T cells where (B) tetramer⁺ and (C) tetramer⁻ CD8⁺ T cells are colored and faceted by weeks p.i. (D) Topic modeling of tumor specific-CD8⁺ T cells profiled by plate based scRNA-seq. Shown is a bar plot of topic scores for top ranked genes (left), and UMAP of the cell profiles (as in A) colored by topic’s weight per cell (right). (E) Heatmap showing the estimate of a linear mixed effect model on the topic (rows) weights by tetramer binding (left), by timepoint for tetramer⁻ (left) and tetramer⁺ (right). (F) Empirical cumulative distribution functions (ECDFs) of topic weights across timepoints (color) and tetramer staining (rows). Average topic weights by timepoint are indicated with vertical dotted lines. TCM – Central Memory, SLEC – Short lived effector, Dysfunc – Dysfunctional, Res - Resident, Reg – Regulatory. (G) UMAP embedding where tumor-specific CD8⁺ T cells are colored by respective signature (as indicated) z-score and tetramer⁻ CD8⁺ T cells in grey. (H) Quantification of signature z-scores as shown in Figure 2G. Violin plot of z-scores across time points. Wilcox-test.

**Figure 3.. TCF-1⁺ tumor-specific CD8 T cells become increasingly dysfunctional over time**
(A) UMAP embedding of tumor specific CD8⁺ T cells (Bodhankar et al.) profiled with droplet-based scRNA-seq colored by cell density and faceted by weeks. (B) Topic modeling identified a precursor-like (Topic 10) and dysfunctional (Topic 8) transcriptional program of tumor-specific CD8⁺ T cells. Shown is a bar plot of topic scores for top ranked genes (left), and UMAP of the cell profiles (as in A) colored by topic’s weight per cell (right). (C) Topic expression correlated with signatures associated with different functional states. Spearman correlation coefficient (color bar) between topic (columns) weights and signature z-score across cells for published signatures (rows) for droplet-based scRNA-seq data. Quie – Quiescent, Eff – Effector, Dys – Dysfunctional. (D-E) TCF-1⁺ tumor specific CD8⁺ T cells decreased in absolute numbers (D) but increased in fraction (E) over tumor development. (D) Number of TCF-1⁺ tumor specific CD8⁺ T cells at indicated timepoints. (E) Representative flow cytometry staining for TCF-1 and Tim-3 on tumor-specific CD8⁺ T cells (left) and % TCF1⁺ of tumor specific CD8⁺ T cells at indicated timepoints (right). (F-G) TCF1⁻ tumor-specific CD8⁺ T cells upregulated number (F) and level (G) of IR expression over time unlike TCF1⁺ tumor-specific CD8⁺ T cells. (F) Percent of tumor-specific CD8⁺ T cells expressing combinations of IR by flow cytometry (TIGIT, PD-1, LAG-3, 2B4). (G) IR geometric MFI at 5 and 16 weeks on tumor-specific CD8⁺ T cells from 1 experiment, representative of 2 experiments (dot: one mouse), Mann-Whitney test. (H-I) Both TCF1^+/− tumor-specific CD8⁺ T cells lost ability to proliferate (H) and produce cytokine (I) with time. (H) Percent Ki-67⁺ of TCF1^+/− tumor-specific CD8⁺ T cells at indicated weeks. (I) Ratio of IFNγ⁺ TNFα⁺ to H-2K^b/SIINFEKL tetramer⁺ of CD8⁺ T cells. Data from at least 3 experiments unless otherwise noted (dot: one mouse), Error bars: SD. *p<0.05, **p<0.01, ***p<0.001, Tukey’s multiple comparisons test unless otherwise noted. NS: non-significant (p>0.05). See also Supplemental Figures 2 and 3.

**Figure 4.. TCF-1⁺ tumor-specific CD8 T cells are transcriptionally diverse and shift over the course of tumor progression**
(A) UMAP embedding of all *Tcf7*⁺ tumor-specific CD8⁺ T cells (Bodhankar et al.) colored by cell density and faceted by time point. (B) Topic modeling of *Tcf7*⁺ tumor-specific CD8⁺ T cells. Shown is a bar plot of topic scores for top ranked genes (left), and UMAP of the cell profiles (as in A) colored by topic’s weight per cell (right). (C) Heatmap showing the estimates per time points (columns) relative to 6 weeks p.i. of a linear mixed effect model on the topic (rows) weights. (D) Only two topics of *Tcf7*⁺ tumor-specific CD8⁺ T cells correlated with reported signatures of precursor-exhausted *Tcf7*⁺ CD8⁺ T cells. Spearman correlation coefficient (color bar) between topic (rows) weights and signature (columns) z-score across cells for published signatures of *Tcf7*⁺ tumor-specific CD8⁺ T cells. (E-F) Data taken from Sade-Feldman et al., 2018. (E) Topics identified in *Tcf7*⁺ tumor-specific CD8⁺ T cells of this manuscript correlated with topics identified in human melanoma patients. Heatmap shows the spearman correlation coefficient (color bar) between human inferred topic (columns) weights and signature z-score when taking top 50 feature genes of mouse topics (rows) across *TCF7*⁺ CD8⁺ T cells of human melanoma patients. (F) Few topics of *TCF7*⁺ CD8⁺ T cells of human melanoma patients correlated with reported signatures of precursor-exhausted *Tcf7*⁺ CD8⁺ T cells in mice. Spearman correlation coefficient (color bar) between topic (rows) weights and signature (columns) z-scores across cells for published signatures for human *Tcf7*⁺ tumor specific CD8⁺ T cells. See also Supplemental Figure 4.

**Figure 5.. SlamF6 expression distinguishes two functionally distinct populations within the TCF-1⁺ population**
(A) *Slamf6* was variably expressed among *Tcf7*⁺ tumor-specific CD8⁺ T cells. UMAP embedding of all *Tcf7*⁺ tumor specific CD8⁺ T cells colored by *Slamf6* expression. (B) Percent SlamF6⁺ of TCF-1⁺ tumor specific CD8⁺ T cells decreased steadily with tumor development. Percent shown by flow cytometry at the indicated week. (C) Percent CCL5⁺ of SlamF6⁺ or SlamF6⁻ TCF-1⁺ tumor-specific CD8⁺ T cells at 8 weeks post-initiation. (D) Geometric MFI of Galectin-3⁺ of SlamF6⁺ or SlamF6⁻ TCF-1⁺ tumor-specific CD8⁺ T cells at 8 weeks post-initiation. (E-F) SlamF6⁺ expressed IR at higher levels (E) and more combinations (F) compared to SlamF6⁻ early. (E) IR geometric MFI at 8 weeks on SlamF6⁺ and SlamF6⁻ TCF-1⁺ tumor specific CD8⁺ T cells from 1 experiment, representative of at least 3 experiments (dot: one mouse), Mann-Whitney test. (F) Percent of tumor-specific SlamF6⁺ or SlamF6⁻ TCF-1⁺ CD8⁺ T cells expressing combinations of IR by flow cytometry (TIGIT, PD-1, LAG-3, 2B4) at indicated week post induction. (G) Percent Ki-67⁺ of SlamF6⁺ or SlamF6⁻ TCF-1⁺ tumor-specific CD8⁺ T cells at indicated week post induction. (H) Ratio of IFNγ⁺ TNFα⁺ SlamF6⁺to SlamF6⁻ TCF-1⁺ CD8⁺ T cells. Data from at least 2 experiments unless otherwise noted (dot: one mouse), Error bars: SD. *p<0.05, **p<0.01, ***p<0.001, Tukey’s multiple comparisons test. NS: non-significant (p>0.05). See also Supplemental Figures 5 and 6.

**Figure 6.. dLN-derived TCF-1⁺ tumor-specific CD8⁺ T cells are continuously recruited to the tumor microenvironment**
(A) Number of tumor-specific CD8⁺ T cells in the dLN remained stable over time. (B) Percent TCF-1⁺ of tumor specific CD8⁺ T cells in the dLN by flow cytometry over time. (C) Percent of tumor-specific CD8⁺ T cells expressing combinations of IRs (color bar) by flow cytometry (TIGIT, PD-1, LAG-3, 2B4) in the dLN. (D) Ratio of IFNγ⁺ TNFβ⁺ to H-2K^b/SIINFEKL tetramer of CD8⁺ T cells over time. (E) % Ki-67⁺ of tumor-specific CD8⁺ T cells in dLN at indicated timepoints. (F) % tumor-specific CD8⁺ T cells of total CD8⁺ T cells in blood at the indicated timepoint. (G) % SlamF6⁺ of TCF-1⁺ tumor-specific CD8⁺ T cells in blood. (H) Blocking egress from dLN; FTY720 experimental schematic. (I) Treating mice with FTY720 significantly reduced fraction of SlamF6⁺ cells, in particular Ki-67⁺ SlamF6⁺, but not SlamF6⁻ cells. From left to right; % TCF-1⁺ of tumor specific CD8⁺ T cells, % SlamF6⁻ TCF-1⁺ of tumor specific CD8⁺ T cells, % SlamF6⁺ TCF-1⁺ of tumor-specific CD8⁺ T cells, and % Ki-67⁺ of SlamF6⁺ TCF-1⁺ tumor-specific CD8⁺ T cells isolated from lungs of untreated or FTY720 treated mice. (J) % SlamF6⁺ or SlamF6⁻ TCF-1⁺ tumor-specific CD8⁺ T cells of total isolated cells in blood of untreated and FTY720 treated mice. Student t-test for I and J. Data from at least 3 experiments unless otherwise noted (dot: one mouse), Error bars: SD. *p<0.05, **p<0.01, ***p<0.001, Tukey’s multiple comparisons test. NS: non-significant (p>0.05). See also Supplemental Figure 7.

**Figure 7.. Migratory cDC1 quantity and quality in the dLN are important for maintaining the SlamF6⁺ TCF-1⁺ tumor-specific CD8⁺ T cell response**
(A) Number of migratory cDC1 isolated from the dLN at the designated timepoint post initiation. (B) Representative histogram showing PD-L1 expression on migratory cDC1 in the dLN node at 5 weeks (blue) and 12 weeks (red), and PD-L1 geometric MFI on migratory cDC1 in the dLN at the indicated timepoints. (C) Percent of cDC1 expressing CD86 by flow cytometry. (D) Boosting cDC1 numbers with Flt3L and agonistic anti-CD40; experimental schematic. (E) Number of migratory cDC1 in the dLN in control or Flt3L/agonistic CD40 treated animal after 1 week of treatment. (F & G) CD86 or PD-L1 geometric MFI on migratory cDC1 in the dLN in control or Flt3L/agonistic anti-CD40 treated KP mice after 1 week of treatment. (H) Total numbers of H-2K^b/SIINFEKL tetramer⁺ CD8⁺ T cells in dLN of control or Flt3L/agonistic anti-CD40 treated KP mice after 1 week of treatment. (I) Total numbers of SlamF6⁺ TCF-1⁺ H-2K^b/SIINFEKL tetramer⁺ CD8 T cells in tumor bearing lungs of control or Flt3L/agonistic anti-CD40 treated KP mice after 1 week of treatment. (J) Extended treatment with Flt3L and anti-CD40 antibody to assess tumor burden; experimental schematic. (K) Percent of total lung occupied by tumor at 8 weeks post induction in mice treated with Flt3L/anti-CD40 treated starting at 6 weeks post-induction or control mice. (L) Percent of total lung occupied by tumor at 16 weeks post induction in mice treated with Flt3L/anti-CD40 treated starting at 14 weeks post-induction or control mice. Tukey’s multiple comparisons test for A and B. Student t-test for D-H. Data from at least 2 experiments or 1 experiment representative of 2 experiments (geometric mean fluorescence intensity analysis) (dot: one mouse), Error bars: SD. *p<0.05, **p<0.001, ***p<0.001, NS: non-significant (p>0.05). See also Supplemental Figure 7.

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References

1. Anderson KG, Mayer-Barber K, Sung H, Beura L, James BR, Taylor JJ, Qunaj L, Griffith TS, Vezys V, Barber DL, and Masopust D (2014). Intravascular staining for discrimination of vascular and tissue leukocytes. Nat Protoc 9, 209–222. - PMC - PubMed
1. Angelosanto JM, Blackburn SD, Crawford A, and Wherry EJ (2012). Progressive loss of memory T cell potential and commitment to exhaustion during chronic viral infection. Journal of virology 86, 8161–8170. - PMC - PubMed
1. Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, Lynn RC, Philip M, Rao A, Restifo NP, et al. (2019). Defining ‘T cell exhaustion’. Nature reviews. Immunology 19, 665–674. - PMC - PubMed
1. Bodhankar S, Chen Y, Lapato A, Dotson AL, Wang J, Vandenbark AA, Saugstad JA, and Offner H (2015). PD-L1 Monoclonal Antibody Treats Ischemic Stroke by Controlling Central Nervous System Inflammation. Stroke 46, 2926–2934. - PMC - PubMed
1. Czechowicz A, Palchaudhuri R, Scheck A, Hu Y, Hoggatt J, Saez B, Pang WW, Mansour MK, Tate TA, Chan YY, et al. (2019). Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10, 617. - PMC - PubMed

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Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1⁺ CD8⁺ T cells in tumor-draining lymph nodes

Affiliations

Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1⁺ CD8⁺ T cells in tumor-draining lymph nodes

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Conflict of interest statement

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