Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2019 Mar;25(3):359-361.
doi: 10.1038/s41591-019-0385-7.

Molecular responses to immune checkpoint blockade in glioblastoma

Hirotaka Ito  1 , Hiroshi Nakashima  1 , E Antonio Chiocca  2
Affiliations
Comment

Molecular responses to immune checkpoint blockade in glioblastoma

Hirotaka Ito et al. Nat Med. 2019 Mar.

Abstract

Transcriptional signatures and immune cell infiltrates associated with immune activation distinguish patients with glioblastoma who initially respond to immune checkpoint blockade from those who do not.

PubMed Disclaimer

Conflict of interest statement

Competing interests

E.A.C is currently an advisor to Advantagene Inc., Alcyone Biosciences, Insightec, Inc., Sigilon Therepeutics and DNAtrix Inc. and has equity interest in DNAtrix; he has also advised Oncorus, Merck, Tocagen, Ziopharm, Stemgen, NanoTx., Ziopharm Oncology, Cerebral Therapeutics, Genenta, Merck, Janssen, Karcinolysis, and Shanaghai Biotech. He has received research support from the National Institutes of Health, the US Department of Defense, American Brain Tumor Association, National Brain Tumor Society, Alliance for Cancer Gene Therapy, Neurosurgical Research Education Foundation, Advantagene, NewLink Genetics, and Amgen. He also is a named inventor on patents related to oncolytic HSV1.

Figures

Fig. 1 |
Fig. 1 |. The molecular responses of GBM to checkpoint blockade.
GBM cells blockade T cell activity by PD-1 and/or PD-L1 signaling. PD-1 blockade, shown in the figure as the gray antibodies, interrupts this signaling, leading to relief of T cell dysfunction. Administration of this therapy before surgery is known as neoadjuvant treatment. Surgical treatment enhances activated T cell infiltration into tumors. Examining continued PD-1 blockade treatment after surgery, the studies in this issue show that therapy-responding GBMs are associated with molecular and cellular markers that are different from those of nonresponsive GBMs. However, over time, even responsive GBMs become nonresponsive because of ongoing immunoediting in which tumor antigens are selected against. TCR, T cell receptor; MHC, major histocompatibility complex.
See this image and copyright information in PMC

Comment on

  • Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma.
    Zhao J, Chen AX, Gartrell RD, Silverman AM, Aparicio L, Chu T, Bordbar D, Shan D, Samanamud J, Mahajan A, Filip I, Orenbuch R, Goetz M, Yamaguchi JT, Cloney M, Horbinski C, Lukas RV, Raizer J, Rae AI, Yuan J, Canoll P, Bruce JN, Saenger YM, Sims P, Iwamoto FM, Sonabend AM, Rabadan R. Zhao J, et al. Nat Med. 2019 Mar;25(3):462-469. doi: 10.1038/s41591-019-0349-y. Epub 2019 Feb 11. Nat Med. 2019. PMID: 30742119 Free PMC article.
  • Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma.
    Schalper KA, Rodriguez-Ruiz ME, Diez-Valle R, López-Janeiro A, Porciuncula A, Idoate MA, Inogés S, de Andrea C, López-Diaz de Cerio A, Tejada S, Berraondo P, Villarroel-Espindola F, Choi J, Gúrpide A, Giraldez M, Goicoechea I, Gallego Perez-Larraya J, Sanmamed MF, Perez-Gracia JL, Melero I. Schalper KA, et al. Nat Med. 2019 Mar;25(3):470-476. doi: 10.1038/s41591-018-0339-5. Epub 2019 Feb 11. Nat Med. 2019. PMID: 30742120 Clinical Trial.
  • Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.
    Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, Wang AC, Ellingson BM, Rytlewski JA, Sanders CM, Kawaguchi ES, Du L, Li G, Yong WH, Gaffey SC, Cohen AL, Mellinghoff IK, Lee EQ, Reardon DA, O'Brien BJ, Butowski NA, Nghiemphu PL, Clarke JL, Arrillaga-Romany IC, Colman H, Kaley TJ, de Groot JF, Liau LM, Wen PY, Prins RM. Cloughesy TF, et al. Nat Med. 2019 Mar;25(3):477-486. doi: 10.1038/s41591-018-0337-7. Epub 2019 Feb 11. Nat Med. 2019. PMID: 30742122 Free PMC article. Clinical Trial.

References

    1. Ostrom QT et al. Neuro. Oncol 20, iv1–iv86 (2018). - PMC - PubMed
    1. Nam JY & de Groot JF J. Oncol. Pract 13, 629–638 (2017). - PubMed
    1. Chiocca EA, Nassiri F, Wang J, Peruzzi P & Zadeh G Neuro. Oncol 21, 14–25 (2019). - PMC - PubMed
    1. Kamiya-Matsuoka C & Gilbert MR CNS Oncol 4, 91–104 (2015). - PMC - PubMed
    1. Dyck L & Mills KH G. Eur. J. Immunol 47, 765–779 (2017). - PubMed