Neoadjuvant immune checkpoint blockade: A window of opportunity to advance cancer immunotherapy
- Cancer Cell. 2023 Sep 11;41(9):1551-1566. doi: 10.1016/j.ccell.2023.07.011.
- 1. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: [email protected].
- 2. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
- 3. Ankyra Therapeutics, Cambridge, MA 02142, USA.
- 4. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: [email protected].
Among new treatment approaches for patients with Cancer, few have accelerated as quickly as neoadjuvant immune checkpoint blockade (ICB). Neoadjuvant Cancer therapy is administered before curative-intent surgery in treatment-naïve patients. Conventional neoadjuvant chemotherapy and radiotherapy are primarily intended to reduce tumor size, improving surgical resectability. However, recent scientific evidence outlined here suggests that neoadjuvant immunotherapy can expand and transcriptionally modify tumor-specific T cell clones to enhance both intratumoral and systemic anti-tumor immunity. It further offers a unique "window of opportunity" to explore mechanisms and identify novel biomarkers of ICB response and resistance, opening possibilities for refining long-term clinical outcome predictions and developing new, more highly effective ICB combination therapies. Here, we examine advances in clinical and scientific knowledge gleaned from studies in select cancers and describe emerging key principles relevant to neoadjuvant ICB across many Cancer types.