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Alternative Checkpoints As Targets For Immunotherapy

Ayush Pant, Ravi Medikonda, M. Lim
Published 2020 · Medicine

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Immunotherapy has shown an unprecedented response in treatment of tumors. However, challenges such as lack of cytotoxic lymphocytes to mount an immune response or development of resistance to therapy can limit efficacy. Here, we discuss alternative checkpoints that can be targeted to improve cytotoxic lymphocyte function while harnessing other components of the immune system. Blockade of alternative checkpoints has improved anti-tumor immunity in mouse models and is being tested clinically with encouraging findings. In addition to modulating T cell function directly, alternative checkpoints can also regulate activity of myeloid cells and regulatory T cells to affect anti-tumor response. Combination of immune checkpoint inhibitors can improve treatment of tumors by activating multiple arms of the immune system.
This paper references
Corrigendum: An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction.
C. Zhu (2015)
Murine B7-H3 Is a Negative Regulator of T Cells1
D. V. Prasad (2004)
CD226 opposes TIGIT to disrupt Tregs in melanoma.
J. Fourcade (2018)
B7-H3 Enhances Tumor Immunity In Vivo by Costimulating Rapid Clonal Expansion of Antigen-Specific CD8+ Cytolytic T Cells1
Liqun Luo (2004)
B 7-H 3 is a potent inhibitor of human T cell activation : No evidence for B 7-H 3 and TREML 2 interaction
J. Leitner (2012)
CEACAM1 regulates TIM-3-mediated tolerance and exhaustion
Yu-Hwa Huang (2015)
The B7 family member B7-H3 preferentially down-regulates T helper type 1–mediated immune responses
Woong-Kyung Suh (2003)
B7‐H3 is a potent inhibitor of human T‐cell activation: No evidence for B7‐H3 and TREML2 interaction
J. Leitner (2009)
B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome.
X. Zang (2007)
Tim‐3/galectin‐9 signaling pathway mediates T‐cell dysfunction and predicts poor prognosis in patients with hepatitis B virus‐associated hepatocellular carcinoma
H. Li (2012)
LAG-3 Regulates Plasmacytoid Dendritic Cell Homeostasis1
C. Workman (2009)
B7-H3: A costimulatory molecule for T cell activation and IFN-γ production
A. Chapoval (2001)
B 7 - H 3 enhances tumor immunity in vivo by costimulating rapid clonal expansion of antigen - specific CD 8 + Cytolytic T cells
L Luo (2004)
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
Liver-primed CD8+ T cells suppress antiviral adaptive immunity through galectin-9-independent T-Cell immunoglobulin and mucin 3 engagement of high-mobility group box 1 in mice
Joseph S. Dolina (2014)
MART-1 peptide vaccination plus IMP321 (LAG-3Ig fusion protein) in patients receiving autologous PBMCs after lymphodepletion: results of a Phase I trial
E. Romano (2013)
Murine b7-h3 is a co-stimulatory molecule for T cell activation.
R. Yan (2013)
The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity
C. Zhu (2005)
Clinical significance and regulation of the costimulatory molecule B 7 - H 3 in human colorectal carcinoma
J Sun (2010)
22:126 cells
An orthotopic colon cancer model for studying the B7-H3 antitumor effect in vivo
C. Lupu (2012)
VISTA Regulates the Development of Protective Antitumor Immunity.
I. Le Mercier (2014)
Initial efficacy of anti-lymphocyte activation gene-3 (anti–LAG-3; BMS-986016) in combination with nivolumab (nivo) in pts with melanoma (MEL) previously treated with anti–PD-1/PD-L1 therapy.
P. Ascierto (2017)
PD - 1 H ( VISTA ) – mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus
X Han (2019)
CD 155 T / TIGIT signaling regulates CD 8 + T - cell metabolism and promotes tumor progression in human gastric cancer
W He
The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity
N. Stanietsky (2009)
Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3
J. Wang (2019)
VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses
L. Wang (2011)
DNAM-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors
S. Gilfillan (2008)
TIGIT and PD-1 impair tumor antigen-specific CD8⁺ T cells in melanoma patients.
Joe-Marc Chauvin (2015)
A phase i study of IMP 321 and gemcitabine as the front - line therapy in patients with advanced pancreatic adenocarcinoma
A Wang-Gillam (2013)
Expression of Tim-3 in gastric cancer tissue and its relationship with prognosis.
G. Cheng (2015)
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Kaori Sakuishi (2010)
Dysfunction of PSA-specific CD8+ T cells in prostate cancer patients correlates with CD38 and Tim-3 expression
Alberto Sada Japp (2015)
VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer
Jianjun Gao (2017)
Biochemical Analysis of the Regulatory T Cell Protein Lymphocyte Activation Gene-3 (LAG-3; CD223)1
N. Li (2004)
A Soluble Lymphocyte Activation Gene-3 Molecule Used as a Vaccine Adjuvant Elicits Greater Humoral and Cellular Immune Responses to Both Particulate and Soluble Antigens1
S. El mir (2000)
Clonal replacement of tumor-specific T cells following PD-1 blockade
K. E. Yost (2019)
A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma
A. Wang-Gillam (2012)
Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer
J. Blando (2019)
Role of LAG-3 in regulatory T cells.
C. Huang (2004)
The co-stimulatory molecule B7-H3 promotes the epithelial-mesenchymal transition in colorectal cancer
B. Jiang (2016)
Clinical importance of B7-H3 expression in human pancreatic cancer
I. Yamato (2009)
A Phase I Pharmacokinetic and Biological Correlative Study of IMP321, a Novel MHC Class II Agonist, in Patients with Advanced Renal Cell Carcinoma
C. Brignone (2009)
Clinical importance of B 7 - H 3 expression in human pancreatic can
I Yamato (2009)
Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape.
Seng-Ryong Woo (2012)
Immunoregulatory protein B7‐H3 promotes growth and decreases sensitivity to therapy in metastatic melanoma cells
K. Flem-Karlsen (2017)
Dual PD 1 / LAG 3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia
M Wierz (2018)
A Dual Role of Graphene Oxide Sheet Deposition on Titanate Nanowire Scaffolds for Osteo-implantation: Mechanical Hardener and Surface Activity Regulator
W. Dong (2015)
Dual PD1/LAG3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia.
Marina Wierz (2018)
Promotion of Tissue Inflammation by the Immune Receptor Tim-3 Expressed on Innate Immune Cells
A. Anderson (2007)
Expression of LAG-3 defines exhaustion of intratumoral PD-1+ T cells and correlates with poor outcome in follicular lymphoma.
Zhi-Zhang Yang (2017)
TIGIT immune checkpoint blockade restores CD8+ T-cell immunity against multiple myeloma.
Camille Guillerey (2018)
Galectin-9 increases Tim-3[+] dendritic cells and CD8[+] T cells and enhances antitumor immunity via galectin-9-Tim-3 interactions
永原 慶子 (2009)
Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients
H. Kakavand (2017)
Tumor-infiltrating NY-ESO-1–specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer
J. Matsuzaki (2010)
Cutting Edge: A Monoclonal Antibody Specific for the Programmed Death-1 Homolog Prevents Graft-versus-Host Disease in Mouse Models
D. Flies (2011)
EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
Tsukasa Shibue (2017)
B7-H3 Negatively Modulates CTL-Mediated Cancer Immunity
K. Yonesaka (2018)
The Tim-3 ligand galectin-9 negatively regulates CD8+ alloreactive T cell and prolongs survival of skin graft.
F. Wang (2007)
CD155T/TIGIT Signaling Regulates CD8+ T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer.
W. He (2017)
LAG‐3 (CD223) reduces macrophage and dendritic cell differentiation from monocyte precursors
S. Buisson (2005)
First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity
C. Brignone (2010)
This study analyzed tumor microenvironment of checkpoint blockade sensitive and resistant tumors (melanoma and pancreatic ductal adenocarcinomas respectively) and identified VISTA as a potent
J Blando (2019)
Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53
K. W. Yoon (2015)
Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation.
M. Nakayama (2009)
Genes that distinguish physiological and pathological angiogenesis.
S. Seaman (2007)
VISTA Is a Novel Broad-Spectrum Negative Checkpoint Regulator for Cancer Immunotherapy
J. L. Lines (2014)
Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages.
J. D. de Groot (2019)
T-Cell Immunoglobulin and ITIM Domain (TIGIT) Associates with CD8+ T-Cell Exhaustion and Poor Clinical Outcome in AML Patients
Y. Kong (2016)
Tumor-expressed B7-H3 mediates the inhibition of antitumor T-cell functions in ovarian cancer insensitive to PD-1 blockade therapy
D. Cai (2019)
TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM
A. Hung (2018)
LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII
Takumi Maruhashi (2018)
Monoclonal antibody-based immunotherapy of ovarian cancer: targeting ovarian cancer cells with the B7-H3-specific mAb 376.96.
J. Fauci (2014)
HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses
H. Yanai (2009)
Cutting Edge: TIGIT Has T Cell-Intrinsic Inhibitory Functions
Nicole Joller (2011)
Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function
Young-hee Lee (2017)
Tumor-infiltrating DCs suppress nucleic acid–mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1
S. Chiba (2012)
VSIG‐3 as a ligand of VISTA inhibits human T‐cell function
J. Wang (2019)
TIGIT predominantly regulates the immune response via regulatory T cells.
S. Kurtuluş (2015)
This study discovered a major ligand for LAG-3 and showed that the ligand FGL1 is upregulated in some human cancers and associates with poot outcomes in anti-PD-1 treated patients
•• Wang (2018)
Apoptosis of tumor infiltrating effector TIM-3+CD8+ T cells in colon cancer
Chiao-Wen Kang (2015)
Targeted deletion of PD-1 in myeloid cells induces antitumor immunity
Laura Strauss (2020)
PD-1H (VISTA)–mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus
Xue Han (2019)
This study showed the expansion of T cells following anti-PD-1 therapy for basal and squamous cell carcinoma were of clones that were not in the tumor prior to treatment
•• Yost (2019)
Murine B 7 - H 3 is a negative regulator of T cells
Prasad DVR (2004)
Expression of LAG‐3 and efficacy of combination treatment with anti‐LAG‐3 and anti‐PD‐1 monoclonal antibodies in glioblastoma
Sarah Harris-Bookman (2018)
Expression of lymphocyte-activating gene 3 and T-cell immunoreceptor with immunoglobulin and ITIM domains in cutaneous melanoma and their correlation with programmed cell death 1 expression in tumor-infiltrating lymphocytes.
W. Lee (2019)
Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma
J. Sun (2010)
Promotion of tissue inflammation by on innate immune cells
AC Anderson (2007)
Defining ‘T cell exhaustion’
C. Blank (2019)
Maturation and Activation of Dendritic Cells Induced by Lymphocyte Activation Gene-3 (CD223)1
S. Andreae (2002)
Metalloproteases regulate T‐cell proliferation and effector function via LAG‐3
N. Li (2007)
The future of immune checkpoint therapy
P. Sharma (2015)
The B 7 family member B 7 - H 3 preferentially down - regulates T helper type 1 - mediated immune responses
WK Suh (2003)
De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation
Hazem E. Ghoneim (2017)
Expression of VISTA correlated with immunosuppression and synergized with CD8 to predict survival in human oral squamous cell carcinoma
L. Wu (2017)
Galectin-9 Increases Tim-3+ Dendritic Cells and CD8+ T Cells and Enhances Antitumor Immunity via Galectin-9-Tim-3 Interactions1
Keiko Nagahara (2008)
Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells
Theodore Kouo (2015)
VISTA expressed in tumour cells regulates T cell function
Kumuluzi Mulati (2018)
The blockade of immune checkpoints in cancer immunotherapy
D. Pardoll (2012)
Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas
Jennifer E. Kim (2016)
Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens
E. Baixeras (1992)
LSECtin expressed on melanoma cells promotes tumor progression by inhibiting antitumor T-cell responses.
F. Xu (2014)
LAG‐3 Protein Expression in Non–Small Cell Lung Cancer and Its Relationship with PD‐1/PD‐L1 and Tumor‐Infiltrating Lymphocytes
Y. He (2017)
The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells
X. Yu (2009)
Diagnosis value of serum B7-H3 expression in non-small cell lung cancer.
G. Zhang (2009)
VISTA is an acidic pH-selective ligand for PSGL-1
Robert J. Johnston (2019)
Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4
Shuang Qin (2019)
Expression of V-domain immunoglobulin suppressor of T cell activation is associated with the advanced stage and presence of lymph node metastasis in ovarian cancer
H. Liao (2018)
B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome
X. Zang (2007)
Murine B 7 - H 3 is a co - stimulatory molecule for T cell activation
R Yan (2013)
Enhanced suppressor function of TIM‐3+FoxP3+ regulatory T cells
A. Gautron (2014)

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