Mixing it up: boosting responses with immunotherapy combinations

Hiroki Komatsuda; Edward S Sim; Ravindra Uppaluri

doi:10.1016/j.trecan.2025.04.013

Mixing it up: boosting responses with immunotherapy combinations

Trends Cancer. 2025 Jun;11(6):496-498. doi: 10.1016/j.trecan.2025.04.013. Epub 2025 May 6.

Authors

Hiroki Komatsuda¹, Edward S Sim², Ravindra Uppaluri³

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
² Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Surgery/Otolaryngology, Brigham and Women's Hospital, Boston, MA, USA; Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Surgery/Otolaryngology, Brigham and Women's Hospital, Boston, MA, USA; Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA. Electronic address: ravindra_uppaluri@dfci.harvard.edu.

PMID: 40335428
PMCID: PMC12158630 (available on 2026-06-01)
DOI: 10.1016/j.trecan.2025.04.013

Abstract

Whether combination neoadjuvant immunotherapy can enhance response in patients with head and neck cancer remains unclear. Recently, Li et al. demonstrated improved responses with neoadjuvant anti-PD-1+CTLA-4 or anti-PD-1+LAG-3 compared with anti-PD-1 monotherapy. These combination strategies act via different mechanisms with distinct biomarkers of response, highlighting the potential for personalized neoadjuvant immunotherapy approaches.

Keywords: head and neck cancer; immune checkpoint inhibitor; neoadjuvant immunotherapy; single-cell RNA sequencing.

MeSH terms

Antineoplastic Combined Chemotherapy Protocols* / pharmacology
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
Biomarkers, Tumor
CTLA-4 Antigen / antagonists & inhibitors
CTLA-4 Antigen / immunology
Head and Neck Neoplasms* / drug therapy
Head and Neck Neoplasms* / immunology
Head and Neck Neoplasms* / pathology
Head and Neck Neoplasms* / therapy
Humans
Immune Checkpoint Inhibitors* / pharmacology
Immune Checkpoint Inhibitors* / therapeutic use
Immunotherapy* / methods
Lymphocyte Activation Gene 3 Protein
Neoadjuvant Therapy / methods
Programmed Cell Death 1 Receptor / antagonists & inhibitors
Programmed Cell Death 1 Receptor / immunology
Treatment Outcome

Substances

Immune Checkpoint Inhibitors
Programmed Cell Death 1 Receptor
CTLA-4 Antigen
PDCD1 protein, human
Lymphocyte Activation Gene 3 Protein
Lag3 protein, human
CTLA4 protein, human
Biomarkers, Tumor

Grants and funding

R01 DE027736/DE/NIDCR NIH HHS/United States