Novel Immune Therapies for Renal Cell Carcinoma: Looking Beyond the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Axes

Eddy Saad; Renée Maria Saliby; Chris Labaki; Wenxin Xu; Srinivas R Viswanathan; David A Braun; Ziad Bakouny

doi:10.1016/j.hoc.2023.05.023

Novel Immune Therapies for Renal Cell Carcinoma: Looking Beyond the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Axes

Hematol Oncol Clin North Am. 2023 Oct;37(5):1027-1040. doi: 10.1016/j.hoc.2023.05.023. Epub 2023 Jun 28.

Authors

Eddy Saad¹, Renée Maria Saliby¹, Chris Labaki², Wenxin Xu¹, Srinivas R Viswanathan³, David A Braun⁴, Ziad Bakouny⁵

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA.
² Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA; Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02115, USA.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
⁴ Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, 300 George Street, Suite 6400, New Haven, CT 06510, USA. Electronic address: David.braun@yale.edu.
⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. Electronic address: ziad_elbakouny@dfci.harvard.edu.

PMID: 37391289
DOI: 10.1016/j.hoc.2023.05.023

Abstract

Immunotherapy has revolutionized treatment for patients with advanced and metastatic renal cell carcinoma. Nevertheless, many patients do not benefit or eventually relapse, highlighting the need for novel immune targets to overcome primary and acquired resistance. This review discusses 2 strategies currently being investigated: disabling inhibitory stimuli that maintain immunosuppression ("brakes") and priming the immune system to target tumoral cells ("gas pedals"). We explore each class of novel immunotherapy, including the rationale behind it, supporting preclinical and clinical evidence, and limitations.

Keywords: Adoptive cell therapies; Cancer vaccines; Cytokines; Immune checkpoints; Immuno-metabolic pathways; Myeloid cell targets; Renal cell carcinoma.

Publication types

Review
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Carcinoma, Renal Cell* / therapy
Humans
Immunotherapy
Kidney Neoplasms* / therapy
Neoplasm Recurrence, Local
Programmed Cell Death 1 Receptor
T-Lymphocytes, Cytotoxic

Substances

Programmed Cell Death 1 Receptor

Grants and funding

P30 CA016359/CA/NCI NIH HHS/United States