Blockade of immune checkpoints in lymph nodes through locoregional delivery augments cancer immunotherapy

David M Francis ¹, Margaret P Manspeaker ¹, Alex Schudel ², Lauren F Sestito ³, Meghan J O'Melia ³, Haydn T Kissick ⁴, Brian P Pollack ⁴, Edmund K Waller ⁴, Susan N Thomas ⁵

Affiliations

¹ School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
² Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
³ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
⁴ Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
⁵ Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA. susan.thomas@gatech.edu.

PMID: 32998971
50 References
33 citations

Abstract

Systemic administration of immune checkpoint blockade (ICB) monoclonal antibodies (mAbs) can unleash antitumor functions of T cells but is associated with variable response rates and off-target toxicities. We hypothesized that antitumor efficacy of ICB is limited by the minimal accumulation of mAb within tissues where antitumor immunity is elicited and regulated, which include the tumor microenvironment (TME) and secondary lymphoid tissues. In contrast to systemic administration, intratumoral and intradermal routes of administration resulted in higher mAb accumulation within both the TME and its draining lymph nodes (LNs) or LNs alone, respectively. The use of either locoregional administration route resulted in pronounced T cell responses from the ICB therapy, which developed in the secondary lymphoid tissues and TME of treated mice. Targeted delivery of mAb to tumor-draining lymph nodes (TdLNs) alone was associated with enhanced antitumor immunity and improved therapeutic effects compared to conventional systemic ICB therapy, and these effects were sustained at reduced mAb doses and comparable to those achieved by intratumoral administration. These data suggest that locoregional routes of administration of ICB mAb can augment ICB therapy by improving immunomodulation within TdLNs.

Other Links

Free PMC article
Full text on Science translational medicine

References
Cited By

References
Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Alena Gros, Maria R Parkhurst, +11 authors, Steven A Rosenberg. less Nat Med, 2016 Feb 24; 22(4). PMID: 26901407 Free PMC article. Highly Cited.
Clonal replacement of tumor-specific T cells following PD-1 blockade. Kathryn E Yost, Ansuman T Satpathy, +13 authors, Howard Y Chang. less Nat Med, 2019 Jul 31; 25(8). PMID: 31359002 Free PMC article. Highly Cited.
Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. Yannick Bulliard, Rose Jolicoeur, +6 authors, Jennifer L Brogdon. less J Exp Med, 2013 Jul 31; 210(9). PMID: 23897982 Free PMC article. Highly Cited.
Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients. Edward Cha, Mark Klinger, +4 authors, Lawrence Fong. less Sci Transl Med, 2014 May 30; 6(238). PMID: 24871131 Free PMC article. Highly Cited.
Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition. Hélène Salmon, Juliana Idoyaga, +19 authors, Miriam Merad. less Immunity, 2016 Apr 21; 44(4). PMID: 27096321 Free PMC article. Highly Cited.
PD-L1 expression on malignant cells is no prerequisite for checkpoint therapy. Jan Willem Kleinovink, Koen A Marijt, +3 authors, Marieke F Fransen. less Oncoimmunology, 2017 May 17; 6(4). PMID: 28507803 Free PMC article. Highly Cited.
Melanoma growth effects on molecular clearance from tumors and biodistribution into systemic tissues versus draining lymph nodes. Nathan Andrew Rohner, Susan Napier Thomas. J Control Release, 2016 Jan 02; 223. PMID: 26721446 Free PMC article.
High-dimensional single cell analysis identifies stem-like cytotoxic CD8+ T cells infiltrating human tumors. Jolanda Brummelman, Emilia M C Mazza, +10 authors, Enrico Lugli. less J Exp Med, 2018 Aug 30; 215(10). PMID: 30154266 Free PMC article. Highly Cited.
Immune Cell Infiltration of the Primary Tumor, Not PD-L1 Status, Is Associated With Improved Response to Checkpoint Inhibition in Metastatic Melanoma. Christiane Kümpers, Mladen Jokic, +6 authors, Patrick Terheyden. less Front Med (Lausanne), 2019 Apr 02; 6. PMID: 30931305 Free PMC article.
Local checkpoint inhibition of CTLA-4 as a monotherapy or in combination with anti-PD1 prevents the growth of murine bladder cancer. Luuk van Hooren, Linda C Sandin, +5 authors, Sara M Mangsbo. less Eur J Immunol, 2016 Nov 23; 47(2). PMID: 27873300
De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation. Hazem E Ghoneim, Yiping Fan, +8 authors, Ben Youngblood. less Cell, 2017 Jun 27; 170(1). PMID: 28648661 Free PMC article. Highly Cited.
Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma. Moshe Sade-Feldman, Keren Yizhak, +32 authors, Nir Hacohen. less Cell, 2018 Nov 06; 175(4). PMID: 30388456 Free PMC article. Highly Cited.
Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Mark J Selby, John J Engelhardt, +4 authors, Alan J Korman. less Cancer Immunol Res, 2014 Apr 30; 1(1). PMID: 24777248 Highly Cited.
Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Brian C Miller, Debattama R Sen, +24 authors, W Nicholas Haining. less Nat Immunol, 2019 Feb 20; 20(3). PMID: 30778252 Free PMC article. Highly Cited.
Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice. Iraklis C Kourtis, Sachiko Hirosue, +4 authors, Melody A Swartz. less PLoS One, 2013 Apr 30; 8(4). PMID: 23626707 Free PMC article.
Localized CD47 blockade enhances immunotherapy for murine melanoma. Jessica R Ingram, Olga S Blomberg, +8 authors, Michael Dougan. less Proc Natl Acad Sci U S A, 2017 Sep 07; 114(38). PMID: 28874561 Free PMC article.
CTLA4 blockade broadens the peripheral T-cell receptor repertoire. Lidia Robert, Jennifer Tsoi, +11 authors, Antoni Ribas. less Clin Cancer Res, 2014 Mar 04; 20(9). PMID: 24583799 Free PMC article. Highly Cited.
Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity. David A Knorr, Rony Dahan, Jeffrey V Ravetch. Proc Natl Acad Sci U S A, 2018 Oct 10; 115(43). PMID: 30297432 Free PMC article.
Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma. Edward W Roberts, Miranda L Broz, +7 authors, Matthew F Krummel. less Cancer Cell, 2016 Jul 19; 30(2). PMID: 27424807 Free PMC article. Highly Cited.
Material design for lymph node drug delivery. Alex Schudel, David M Francis, Susan N Thomas. Nat Rev Mater, 2020 Jun 12; 4(6). PMID: 32523780 Free PMC article.
PD-1 blockade induces responses by inhibiting adaptive immune resistance. Paul C Tumeh, Christina L Harview, +23 authors, Antoni Ribas. less Nature, 2014 Nov 28; 515(7528). PMID: 25428505 Free PMC article. Highly Cited.
Eradication of spontaneous malignancy by local immunotherapy. Idit Sagiv-Barfi, Debra K Czerwinski, +4 authors, Ronald Levy. less Sci Transl Med, 2018 Feb 02; 10(426). PMID: 29386357 Free PMC article. Highly Cited.
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Spencer C Wei, Colm R Duffy, James P Allison. Cancer Discov, 2018 Aug 18; 8(9). PMID: 30115704 Highly Cited. Review.
Tremelimumab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells. Sameena Khan, Deborah J Burt, +3 authors, Eyad Elkord. less Clin Immunol, 2010 Nov 09; 138(1). PMID: 21056008
Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response. Pia Kvistborg, Daisy Philips, +13 authors, Ton N Schumacher. less Sci Transl Med, 2014 Sep 19; 6(254). PMID: 25232180 Highly Cited.
Transcytosis route mediates rapid delivery of intact antibodies to draining lymph nodes. Laura Kähäri, Ruth Fair-Mäkelä, +4 authors, Marko Salmi. less J Clin Invest, 2019 Jun 25; 129(8). PMID: 31232704 Free PMC article.
Intratumoral immunotherapy: using the tumor as the remedy. A Marabelle, L Tselikas, T de Baere, R Houot. Ann Oncol, 2017 Dec 19; 28(suppl_12). PMID: 29253115 Review.
Human Lymph Nodes Maintain TCF-1hi Memory T Cells with High Functional Potential and Clonal Diversity throughout Life. Michelle Miron, Brahma V Kumar, +13 authors, Donna L Farber. less J Immunol, 2018 Aug 17; 201(7). PMID: 30111633 Free PMC article.
At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. Andrew M Intlekofer, Craig B Thompson. J Leukoc Biol, 2013 Apr 30; 94(1). PMID: 23625198 Free PMC article. Highly Cited. Review.
An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Caroline S Jansen, Nataliya Prokhnevska, +26 authors, Haydn Kissick. less Nature, 2019 Dec 13; 576(7787). PMID: 31827286 Free PMC article. Highly Cited.
Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Jedd D Wolchok, Bart Neyns, +14 authors, Celeste Lebbé. less Lancet Oncol, 2009 Dec 17; 11(2). PMID: 20004617 Highly Cited.
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok. less N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431 Free PMC article. Highly Cited.
Subcutaneous absorption of monoclonal antibodies: role of dose, site of injection, and injection volume on rituximab pharmacokinetics in rats. Leonid Kagan, Michael R Turner, Sathy V Balu-Iyer, Donald E Mager. Pharm Res, 2011 Sep 03; 29(2). PMID: 21887597
Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Alice O Kamphorst, Andreas Wieland, +17 authors, Rafi Ahmed. less Science, 2017 Mar 11; 355(6332). PMID: 28280249 Free PMC article. Highly Cited.
Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Se Jin Im, Masao Hashimoto, +13 authors, Rafi Ahmed. less Nature, 2016 Aug 09; 537(7620). PMID: 27501248 Free PMC article. Highly Cited.
Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3+ Regulatory T Cells (Tregs) in Human Cancers. Anu Sharma, Sumit K Subudhi, +6 authors, Padmanee Sharma. less Clin Cancer Res, 2018 Jul 29; 25(4). PMID: 30054281 Free PMC article. Highly Cited.
Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors. Kristian M Hargadon, Coleman E Johnson, Corey J Williams. Int Immunopharmacol, 2018 Jul 11; 62. PMID: 29990692 Highly Cited. Review.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada. less J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981 Free PMC article. Highly Cited.
The blockade of immune checkpoints in cancer immunotherapy. Drew M Pardoll. Nat Rev Cancer, 2012 Mar 23; 12(4). PMID: 22437870 Free PMC article. Highly Cited. Review.
Subcutaneous delivery of monoclonal antibodies: How do we get there? Margarida Viola, Joana Sequeira, +4 authors, António J Ribeiro. less J Control Release, 2018 Aug 06; 286. PMID: 30077735 Review.
Systemic Immunity Is Required for Effective Cancer Immunotherapy. Matthew H Spitzer, Yaron Carmi, +10 authors, Edgar G Engleman. less Cell, 2017 Jan 24; 168(3). PMID: 28111070 Free PMC article. Highly Cited.
Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Greg M Thurber, Michael M Schmidt, K Dane Wittrup. Adv Drug Deliv Rev, 2008 Jun 11; 60(12). PMID: 18541331 Free PMC article. Highly Cited. Review.
Progress and opportunities for enhancing the delivery and efficacy of checkpoint inhibitors for cancer immunotherapy. David M Francis, Susan N Thomas. Adv Drug Deliv Rev, 2017 Apr 30; 114. PMID: 28455187 Free PMC article. Review.
Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Kristen E Pauken, Morgan A Sammons, +16 authors, E John Wherry. less Science, 2016 Oct 30; 354(6316). PMID: 27789795 Free PMC article. Highly Cited.
Controlled local delivery of CTLA-4 blocking antibody induces CD8+ T-cell-dependent tumor eradication and decreases risk of toxic side effects. Marieke F Fransen, Tetje C van der Sluis, +2 authors, Ferry Ossendorp, Ramon Arens, Cornelis J M Melief. less Clin Cancer Res, 2013 Jun 22; 19(19). PMID: 23788581
Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory. Mauro Poggio, Tianyi Hu, +8 authors, Robert Blelloch. less Cell, 2019 Apr 06; 177(2). PMID: 30951669 Free PMC article. Highly Cited.
Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. Omid Hamid, Caroline Robert, +23 authors, Antoni Ribas. less N Engl J Med, 2013 Jun 04; 369(2). PMID: 23724846 Free PMC article. Highly Cited.
Tumor-draining lymph nodes are pivotal in PD-1/PD-L1 checkpoint therapy. Marieke F Fransen, Mark Schoonderwoerd, +5 authors, Ferry Ossendorp. less JCI Insight, 2018 Dec 07; 3(23). PMID: 30518694 Free PMC article. Highly Cited.
PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. Vikram R Juneja, Kathleen A McGuire, +5 authors, Arlene H Sharpe. less J Exp Med, 2017 Mar 18; 214(4). PMID: 28302645 Free PMC article. Highly Cited.
Assessment of Subcutaneous vs Intravenous Administration of Anti-PD-1 Antibody PF-06801591 in Patients With Advanced Solid Tumors: A Phase 1 Dose-Escalation Trial. Melissa L Johnson, Fadi Braiteh, +7 authors, Siwen Hu-Lieskovan. less JAMA Oncol, 2019 May 31; 5(7). PMID: 31145415 Free PMC article.

Citedby
Lymphatic immunomodulation using engineered drug delivery systems for cancer immunotherapy. Margaret P Manspeaker, Susan N Thomas. Adv Drug Deliv Rev, 2020 Oct 16; 160. PMID: 33058931 Free PMC article. Systematic Review.
Quality of CD8+ T cell immunity evoked in lymph nodes is compartmentalized by route of antigen transport and functional in tumor context. M J O'Melia, N A Rohner, +3 authors, S N Thomas. less Sci Adv, 2020 Dec 15; 6(50). PMID: 33310857 Free PMC article.
Tumor-draining lymph nodes are survival niches that support T cell priming against lymphatic transported tumor antigen and effects of immune checkpoint blockade in TNBC. Meghan J O'Melia, Margaret P Manspeaker, Susan N Thomas. Cancer Immunol Immunother, 2021 Jan 19; 70(8). PMID: 33459842 Free PMC article.
In Situ Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy. Jihoon Kim, David M Francis, Susan N Thomas. Nanomaterials (Basel), 2021 Mar 07; 11(2). PMID: 33673289 Free PMC article.
Immunotherapy Goes Local: The Central Role of Lymph Nodes in Driving Tumor Infiltration and Efficacy. Kim M van Pul, Marieke F Fransen, Rieneke van de Ven, Tanja D de Gruijl. Front Immunol, 2021 Mar 19; 12. PMID: 33732264 Free PMC article. Review.
Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies. I-Tsu Chyuan, Ching-Liang Chu, Ping-Ning Hsu. Cancers (Basel), 2021 Apr 04; 13(6). PMID: 33801815 Free PMC article. Review.
Locally Advanced Pancreatic Cancer: Percutaneous Management Using Ablation, Brachytherapy, Intra-arterial Chemotherapy, and Intra-tumoral Immunotherapy. Florentine E F Timmer, Bart Geboers, +7 authors, Martijn R Meijerink. less Curr Oncol Rep, 2021 Apr 18; 23(6). PMID: 33864144 Free PMC article. Review.
Intratumoural administration and tumour tissue targeting of cancer immunotherapies. Ignacio Melero, Eduardo Castanon, +2 authors, Maite Alvarez, Stephane Champiat, Aurelien Marabelle. less Nat Rev Clin Oncol, 2021 May 20; 18(9). PMID: 34006998 Free PMC article. Review.
Importance of lymph node immune responses in MSI-H/dMMR colorectal cancer. Koji Inamori, Yosuke Togashi, +13 authors, Hiroyoshi Nishikawa. less JCI Insight, 2021 Mar 24; 6(9). PMID: 33755600 Free PMC article.
Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement. Ai Lin Chin, Shan Jiang, +4 authors, Rong Tong. less Nat Commun, 2021 Aug 28; 12(1). PMID: 34446702 Free PMC article.
Pancreatic Cancer and Immunotherapy: A Clinical Overview. Florentine E F Timmer, Bart Geboers, +12 authors, Tanja D de Gruijl. less Cancers (Basel), 2021 Aug 28; 13(16). PMID: 34439292 Free PMC article. Review.
Immune Checkpoint Therapy: Tumor Draining Lymph Nodes in the Spotlights. Marieke F Fransen, Thorbald van Hall, Ferry Ossendorp. Int J Mol Sci, 2021 Sep 11; 22(17). PMID: 34502307 Free PMC article. Review.
Translational Applications of Hydrogels. Santiago Correa, Abigail K Grosskopf, +4 authors, Eric A Appel. less Chem Rev, 2021 May 04; 121(18). PMID: 33938724 Free PMC article. Review.
Strategies to sensitize cancer cells to immunotherapy. Andrew George, Ilyas Sahin, +3 authors, Wafik S El-Deiry. less Hum Vaccin Immunother, 2021 May 22; 17(8). PMID: 34019474 Free PMC article.
Motility Dynamics of T Cells in Tumor-Draining Lymph Nodes: A Rational Indicator of Antitumor Response and Immune Checkpoint Blockade. Yasuhiro Kanda, Taku Okazaki, Tomoya Katakai. Cancers (Basel), 2021 Sep 29; 13(18). PMID: 34572844 Free PMC article. Review.
Lymph Node-Targeted Synthetically Glycosylated Antigen Leads to Antigen-Specific Immunological Tolerance. Chitavi D Maulloo, Shijie Cao, +8 authors, Jeffrey A Hubbell. less Front Immunol, 2021 Oct 12; 12. PMID: 34630389 Free PMC article.
Overcoming physical stromal barriers to cancer immunotherapy. Seung Woo Chung, Yunxuan Xie, Jung Soo Suk. Drug Deliv Transl Res, 2021 Aug 06; 11(6). PMID: 34351575 Free PMC article. Review.
A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing antitumor immune response. Kelli A Connolly, Manik Kuchroo, +19 authors, Nikhil S Joshi. less Sci Immunol, 2021 Oct 02; 6(64). PMID: 34597124 Free PMC article.
Tumor-draining lymph nodes: At the crossroads of metastasis and immunity. Haley du Bois, Taylor A Heim, Amanda W Lund. Sci Immunol, 2021 Sep 14; 6(63). PMID: 34516744 Free PMC article. Review.
Drug-eluting immune checkpoint blockade antibody-nanoparticle conjugate enhances locoregional and systemic combination cancer immunotherapy through T lymphocyte targeting. David M Francis, Margaret P Manspeaker, +4 authors, Susan N Thomas. less Biomaterials, 2021 Oct 23; 279. PMID: 34678650 Free PMC article.
Combinatorial immunotherapy induces tumor-infiltrating CD8+ T cells with distinct functional, migratory, and stem-like properties. Natalija Van Braeckel-Budimir, Joseph Samuel Dolina, +14 authors, Shahram Salek-Ardakani. less J Immunother Cancer, 2021 Dec 15; 9(12). PMID: 34903555 Free PMC article.
Immune landscape in vulvar cancer-draining lymph nodes indicates distinct immune escape mechanisms in support of metastatic spread and growth. Anne Marijne Heeren, Jossie Rotman, +7 authors, Tanja D de Gruijl. less J Immunother Cancer, 2021 Oct 27; 9(10). PMID: 34697217 Free PMC article.
Maximizing response to intratumoral immunotherapy in mice by tuning local retention. Noor Momin, Joseph R Palmeri, +8 authors, K Dane Wittrup. less Nat Commun, 2022 Jan 12; 13(1). PMID: 35013154 Free PMC article.
The Role of m6A Epigenetic Modification in the Treatment of Colorectal Cancer Immune Checkpoint Inhibitors. Huan Tong, He Wei, Alhaji Osman Smith, Juan Huang. Front Immunol, 2022 Jan 25; 12. PMID: 35069586 Free PMC article. Review.
Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes. Noelle Leary, Sarina Walser, +8 authors, Lothar C Dieterich. less J Extracell Vesicles, 2022 Feb 22; 11(2). PMID: 35188342 Free PMC article.
Immunotherapeutic Approaches for the Treatment of HPV-Associated (Pre-)Cancer of the Cervix, Vulva and Penis. Tynisha S Rafael, Jossie Rotman, +5 authors, Ekaterina S Jordanova. less J Clin Med, 2022 Feb 26; 11(4). PMID: 35207374 Free PMC article. Review.
Synthetic Matrix Scaffolds Engineer the In Vivo Tumor Immune Microenvironment for Immunotherapy Screening. Meghan J O'Melia, Adriana Mulero-Russe, +7 authors, Susan N Thomas. less Adv Mater, 2022 Jan 07; 34(10). PMID: 34989049 Free PMC article.
Thermosensitive hydrogel releasing nitric oxide donor and anti-CTLA-4 micelles for anti-tumor immunotherapy. Jihoon Kim, David M Francis, +4 authors, Susan N Thomas. less Nat Commun, 2022 Mar 20; 13(1). PMID: 35304456 Free PMC article.
Innate lymphoid cells: NK and cytotoxic ILC3 subsets infiltrate metastatic breast cancer lymph nodes. Louise Rethacker, Maxime Boy, +9 authors, Anne Caignard. less Oncoimmunology, 2022 Apr 05; 11(1). PMID: 35371620 Free PMC article.
The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development. Zacharias Fasoulakis, Antonios Koutras, +14 authors, Emmanuel N Kontomanolis. less Cancers (Basel), 2022 Apr 13; 14(7). PMID: 35406423 Free PMC article. Review.
Tumor-Draining Lymph Node Reconstruction Promotes B Cell Activation During E0771 Mouse Breast Cancer Growth. Dante Alexander Patrick Louie, Darellynn Oo, +5 authors, Shan Liao. less Front Pharmacol, 2022 Apr 15; 13. PMID: 35418862 Free PMC article.
Standing Watch: Immune Activation and Failure in Melanoma Sentinel Lymph Nodes. Amanda W Lund. Clin Cancer Res, 2022 Mar 10; 28(10). PMID: 35262676 Free PMC article.
Tumor-derived IL-8 facilitates lymph node metastasis of gastric cancer via PD-1 up-regulation in CD8+ T cells. Xiang Li, Jing Zhai, +5 authors, Lizong Shen. less Cancer Immunol Immunother, 2022 May 29;. PMID: 35633411

BioKDE: Biomedical Knowledge Discovery Engine

Abstract

Other Links