Impact of anatomic site on antigen-presenting cells in cancer

Checkpoint blockade immunotherapy (CBT) can induce long-term clinical benefits in patients with advanced cancer; however, response rates to CBT vary by cancer type. Cancers of the skin, lung, and kidney are largely responsive to CBT, while cancers of the pancreas, ovary, breast, and metastatic lesions to the liver respond poorly. The impact of tissue-resident immune cells on antitumor immunity is an emerging area of investigation. Recent evidence indicates that antitumor immune responses and efficacy of CBT depend on the tissue site of the tumor lesion. As myeloid cells are predominantly tissue-resident and can shape tumor-reactive T cell responses, it is conceivable that tissue-specific differences in their function underlie the tissue-site-dependent variability in CBT responses. Understanding the roles of tissue-specific myeloid cells in antitumor immunity can open new avenues for treatment design. In this review, we discuss the roles of tissue-specific antigen-presenting cells (APCs) in governing antitumor immune responses, with a particular focus on the contributions of tissue-specific dendritic cells. Using the framework of the Cancer-Immunity Cycle, we examine the contributions of tissue-specific APC in CBT-sensitive and CBT-resistant carcinomas, highlight how these cells can be therapeutically modulated, and identify gaps in knowledge that remain to be addressed.

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The impact of antigen expression in antigen-presenting cells on humoral immune responses against the transgene product

Gene Therapy ◽

10.1038/gt.2009.125 ◽

2009 ◽

Vol 17 (2) ◽

pp. 288-293 ◽

Cited By ~ 5

Author(s):

Y Feng ◽

F Jacobs ◽

E Van Craeyveld ◽

J Lievens ◽

J Snoeys ◽

...

Keyword(s):

Immune Responses ◽

Antigen Presenting Cells ◽

Antigen Expression ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Antigen Presenting ◽

The Impact

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Multi-Immune Agonist Nanoparticle Therapy Stimulates Type I Interferons to Activate Antigen-Presenting Cells and Induce Antigen-Specific Antitumor Immunity

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.0c00984 ◽

2021 ◽

Vol 18 (3) ◽

pp. 1014-1025

Author(s):

Elizabeth S. Levy ◽

Ryan Chang ◽

Colin R. Zamecnik ◽

Miqdad O. Dhariwala ◽

Lawrence Fong ◽

...

Keyword(s):

Antitumor Immunity ◽

Antigen Presenting Cells ◽

Type I Interferons ◽

Type I ◽

Antigen Presenting

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TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Activate CD4 T Cells

Cells ◽

10.3390/cells9051317 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1317 ◽

Cited By ~ 1

Author(s):

Alba Martínez ◽

Cristina Bono ◽

Daniel Gozalbo ◽

Helen S. Goodridge ◽

M. Luisa Gil ◽

...

Keyword(s):

Bone Marrow ◽

Progenitor Cells ◽

Proinflammatory Cytokine ◽

Cytokine Production ◽

Antigen Presenting Cells ◽

Proinflammatory Cytokine Production ◽

Hematopoietic Stem ◽

Stem And Progenitor Cells ◽

Antigen Presenting ◽

The Impact

Microbial recognition by pattern recognition receptors (PRRs) expressed on hematopoietic stem and progenitor cells (HSPCs) not only activates myelopoiesis but also programs the function of the monocytes and macrophages they produce. For instance, changes in HSPC programming modify the ability of macrophages derived from them to produce inflammatory cytokines. While HSPCs exposed to a TLR2 agonist give rise to tolerized macrophages (lower proinflammatory cytokine production), HSPCs treated with Dectin-1 ligands produce trained macrophages (higher proinflammatory cytokine production). However, nothing is known about the impact of HSPC exposure to microbes on the function of antigen presenting cells (APCs). In this study we evaluated whether treatment of murine bone marrow HSPCs with a TLR2 or Dectin-1 ligand impacts the antigen presenting capacity of APCs derived from them in vitro. Following activation with microbial ligands or Candida albicans yeasts, APCs derived from TLR2/Dectin-1-programed HSPCs exhibit altered expression of MHCII (signal 1), co-stimulatory molecules (CD40, CD80 and CD86; signal 2) and cytokines (TNF-α, IL-6, IL-12 p40 and IL-2; signal 3). Moreover, APCs derived from TLR2/Dectin-1-programed HSPCs prime enhanced Th1 and Th17 responses, which are important for antifungal defense, in CD4 T cell cocultures. Overall, these results demonstrate for the first time that microbial detection by bone marrow HSPCs can modulate the adaptive immune response by inducing the production of APCs with an altered phenotype.

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Regulation of Antitumor Immune Responses by the IL-12 Family Cytokines, IL-12, IL-23, and IL-27

Clinical and Developmental Immunology ◽

10.1155/2010/832454 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 80

Author(s):

Mingli Xu ◽

Izuru Mizoguchi ◽

Noriko Morishima ◽

Yukino Chiba ◽

Junichiro Mizuguchi ◽

...

Keyword(s):

T Cells ◽

Immune Responses ◽

Th17 Cells ◽

Antitumor Immunity ◽

Inflammatory Responses ◽

Memory T Cells ◽

Th1 Cells ◽

Signal Transducers ◽

Th Cell ◽

Antigen Presenting

The interleukin (IL)-12 family, which is composed of heterodimeric cytokines including IL-12, IL-23, and IL-27, is produced by antigen-presenting cells such as macrophages and dendritic cells and plays critical roles in the regulation of helper T (Th) cell differentiation. IL-12 induces IFN- production by NK and T cells and differentiation to Th1 cells. IL-23 induces IL-17 production by memory T cells and expands and maintains inflammatory Th17 cells. IL-27 induces the early Th1 differentiation and generation of IL-10-producing regulatory T cells. In addition, these cytokines induce distinct immune responses to tumors. IL-12 activates signal transducers and activator of transcription (STAT)4 and enhances antitumor cellular immunity through interferon (IFN)- production. IL-27 activates STAT1, as does IFN- and STAT3 as well, and enhances antitumor immunity by augmenting cellular and humoral immunities. In contrast, although exogenously overexpressed IL-23 enhances antitumor immunity via memory T cells, endogenous IL-23 promotes protumor immunity through STAT3 activation by inducing inflammatory responses including IL-17 production.

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Impact of surface chemistry and topography on the function of antigen presenting cells

Biomaterials Science ◽

10.1039/c4bm00375f ◽

2015 ◽

Vol 3 (3) ◽

pp. 424-441 ◽

Cited By ~ 47

Author(s):

H. M. Rostam ◽

S. Singh ◽

N. E. Vrana ◽

M. R. Alexander ◽

A. M. Ghaemmaghami

Keyword(s):

Surface Chemistry ◽

Surface Topography ◽

Antigen Presenting Cells ◽

Biomaterial Surface ◽

And Function ◽

Antigen Presenting ◽

The Impact

The impact of biomaterial surface topography and chemistry on antigen presenting cells’ phenotype and function.

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Altered Humoral Immune Responses and IgG Subtypes in NOX2-Deficient Mice and Patients: A Key Role for NOX2 in Antigen-Presenting Cells

Frontiers in Immunology ◽

10.3389/fimmu.2018.01555 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Julien Cachat ◽

Christine Deffert ◽

Marco Alessandrini ◽

Pascale Roux-Lombard ◽

Audrey Le Gouellec ◽

...

Keyword(s):

Immune Responses ◽

Antigen Presenting Cells ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Antigen Presenting ◽

Deficient Mice

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Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells

Blood ◽

10.1182/blood-2007-09-113522 ◽

2008 ◽

Vol 111 (7) ◽

pp. 3546-3552 ◽

Cited By ~ 33

Author(s):

Christian Schütz ◽

Martin Fleck ◽

Andreas Mackensen ◽

Alessia Zoso ◽

Dagmar Halbritter ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Fas Ligand ◽

T Cell Responses ◽

Antigen Presenting Cells ◽

Cytotoxic T Cell ◽

Cell Responses ◽

Cytotoxic T Cell Responses ◽

Antigen Presenting

Abstract Several cell-based immunotherapy strategies have been developed to specifically modulate T cell–mediated immune responses. These methods frequently rely on the utilization of tolerogenic cell–based antigen-presenting cells (APCs). However, APCs are highly sensitive to cytotoxic T-cell responses, thus limiting their therapeutic capacity. Here, we describe a novel bead-based approach to modulate T-cell responses in an antigen-specific fashion. We have generated killer artificial APCs (κaAPCs) by coupling an apoptosis-inducing α-Fas (CD95) IgM mAb together with HLA-A2 Ig molecules onto beads. These κaAPCs deplete targeted antigen-specific T cells in a Fas/Fas ligand (FasL)–dependent fashion. T-cell depletion in cocultures is rapidly initiated (30 minutes), dependent on the amount of κaAPCs and independent of activation-induced cell death (AICD). κaAPCs represent a novel technology that can control T cell–mediated immune responses, and therefore has potential for use in treatment of autoimmune diseases and allograft rejection.

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