. 2017 Dec; 18(12):.
doi: 10.3390/ijms18122642.

Newly Emerging Immune Checkpoints: Promises for Future Cancer Therapy

Robert J Torphy 1 Richard D Schulick 2 Yuwen Zhu 3 
  • PMID: 29211042
  •     87 References
  •     37 citations


Cancer immunotherapy has been a great breakthrough, with immune checkpoint inhibitors leading the way. Despite the clinical effectiveness of certain immune checkpoint inhibitors, the overall response rate remains low, and the effectiveness of immunotherapies for many tumors has been disappointing. There is substantial interest in looking for additional immune checkpoint molecules that may act as therapeutic targets for cancer. Recent advances during the last decade have identified several novel immune checkpoint targets, including lymphocyte activation gene-3 (LAG-3), B and T lymphocyte attenuator (BTLA), programmed death-1 homolog (PD-1H), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIM-3)/carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), and the poliovirus receptor (PVR)-like receptors. The investigations into these molecules have generated promising results in preclinical studies. Herein, we will summarize our current progress and understanding of these newly-characterized immune checkpoints and their potential application in cancer immunotherapy.

Keywords: cosignaling; immune checkpoints; immunotherapy.

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Onco Targets Ther, 2020 Aug 18; 13. PMID: 32801772    Free PMC article.
Targeted Therapies and Immune-Checkpoint Inhibition in Head and Neck Squamous Cell Carcinoma: Where Do We Stand Today and Where to Go?
Jens von der Grün, Franz Rödel, +4 authors, Panagiotis Balermpas.
Cancers (Basel), 2019 Apr 17; 11(4). PMID: 30987257    Free PMC article.
Enhancing Dendritic Cell Therapy in Solid Tumors with Immunomodulating Conventional Treatment.
Robert A Belderbos, Joachim G J V Aerts, Heleen Vroman.
Mol Ther Oncolytics, 2019 Apr 26; 13. PMID: 31020037    Free PMC article.
Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy.
Yuqing Cao, Xiaoyu Wang, +5 authors, Feng Xu.
Signal Transduct Target Ther, 2020 Oct 31; 5(1). PMID: 33122640    Free PMC article.
Polysaccharides Derived from Saposhnikovia divaricata May Suppress Breast Cancer Through Activating Macrophages.
Jingxian Ding, Yonghong Guo, +5 authors, Yali Cao.
Onco Targets Ther, 2020 Nov 03; 13. PMID: 33132702    Free PMC article.
Immunotherapies in ovarian cancer.
Elena García-Martínez, J Alejandro Pérez-Fidalgo.
EJC Suppl, 2020 Nov 27; 15. PMID: 33240447    Free PMC article.
Targeting Immune Checkpoints in Lung Cancer: Current Landscape and Future Prospects.
Long Long, Chen Zhao, +3 authors, Honglei Chen.
Clin Drug Investig, 2019 Feb 20; 39(4). PMID: 30778885
Targeting Tumor Microenvironment for Cancer Therapy.
Catarina Roma-Rodrigues, Rita Mendes, Pedro V Baptista, Alexandra R Fernandes.
Int J Mol Sci, 2019 Feb 20; 20(4). PMID: 30781344    Free PMC article.
Highly Cited. Review.
Natural Killer Immunotherapy for Minimal Residual Disease Eradication Following Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia.
Norimichi Hattori, Tsuyoshi Nakamaki.
Int J Mol Sci, 2019 Apr 28; 20(9). PMID: 31027331    Free PMC article.
Small molecules targeting the innate immune cGAS‒STING‒TBK1 signaling pathway.
Chunyong Ding, Zilan Song, +2 authors, Ao Zhang.
Acta Pharm Sin B, 2020 Dec 24; 10(12). PMID: 33354501    Free PMC article.
Personalized Immuno-Oncology.
Kewal K Jain.
Med Princ Pract, 2020 Aug 26; 30(1). PMID: 32841942    Free PMC article.
Transcriptomic Profiling of Fibropapillomatosis in Green Sea Turtles (Chelonia mydas) From South Texas.
Nicholas B Blackburn, Ana Cristina Leandro, +10 authors, Joanne E Curran.
Front Immunol, 2021 Mar 16; 12. PMID: 33717164    Free PMC article.
Evolutionary genetic algorithm identifies IL2RB as a potential predictive biomarker for immune-checkpoint therapy in colorectal cancer.
Matthew Alderdice, Stephanie G Craig, +12 authors, Darragh G McArt.
NAR Genom Bioinform, 2021 May 01; 3(2). PMID: 33928242    Free PMC article.
Obesity results in adipose tissue T cell exhaustion.
Cara E Porsche, Jennifer B Delproposto, +2 authors, Carey N Lumeng.
JCI Insight, 2021 Mar 17; 6(8). PMID: 33724954    Free PMC article.
Clinical Insights Into Novel Immune Checkpoint Inhibitors.
Jii Bum Lee, Sang-Jun Ha, Hye Ryun Kim.
Front Pharmacol, 2021 May 25; 12. PMID: 34025438    Free PMC article.
VISTA: A Promising Target for Cancer Immunotherapy?
Marco Tagliamento, Elisa Agostinetto, +4 authors, Matteo Lambertini.
Immunotargets Ther, 2021 Jul 01; 10. PMID: 34189130    Free PMC article.
The GPR171 pathway suppresses T cell activation and limits antitumor immunity.
Yuki Fujiwara, Robert J Torphy, +8 authors, Yuwen Zhu.
Nat Commun, 2021 Oct 08; 12(1). PMID: 34615877    Free PMC article.
Immune Profiling of Medullary Thyroid Cancer-An Opportunity for Immunotherapy.
Kinga Hińcza-Nowak, Artur Kowalik, +7 authors, Aldona Kowalska.
Genes (Basel), 2021 Oct 24; 12(10). PMID: 34680929    Free PMC article.
VISTA inhibitors in cancer immunotherapy: a short perspective on recent progresses.
Chenyang Wu, Xin Cao, Xiaojin Zhang.
RSC Med Chem, 2021 Nov 16; 12(10). PMID: 34778768    Free PMC article.
Circular RNA hsa_circ_0000190 Facilitates the Tumorigenesis and Immune Evasion by Upregulating the Expression of Soluble PD-L1 in Non-Small-Cell Lung Cancer.
Yung-Hung Luo, Yi-Ping Yang, +8 authors, Shih-Hwa Chiou.
Int J Mol Sci, 2022 Jan 12; 23(1). PMID: 35008490    Free PMC article.
Modulation of intrinsic inhibitory checkpoints using nano-carriers to unleash NK cell activity.
Guy Biber, Batel Sabag, +7 authors, Mira Barda-Saad.
EMBO Mol Med, 2021 Nov 03; 14(1). PMID: 34725941    Free PMC article.
Intratumoral expression analysis reveals that OX40 and TIM-3 are prominently expressed and have variable associations with clinical outcomes in high grade serous ovarian cancer.
Nicole E James, Ashley D Valenzuela, +5 authors, Jennifer R Ribeiro.
Oncol Lett, 2022 May 10; 23(6). PMID: 35527785    Free PMC article.