Neoadjuvant immunotherapy refers to the administration of immunotherapeutic agents, most commonly immune checkpoint inhibitors, prior to definitive surgical resection in patients with resectable malignancies.
The primary goals are to induce tumor regression, eradicate micrometastatic disease, and enhance systemic antitumor immunity, potentially improving long-term outcomes such as relapse-free and overall survival compared to surgery alone or adjuvant therapy.
Mechanistically, neoadjuvant immunotherapy leverages the presence of the intact tumor to stimulate a robust, antigen-specific T-cell response, which may persist after surgery and target residual disease.
This approach has demonstrated high pathologic response rates and favorable survival outcomes in several tumor types, including melanoma, non-small cell lung cancer (NSCLC), and triple-negative breast cancer, head and neck squamous cell cancer, with recent FDA approvals for neoadjuvant immune checkpoint inhibitors in early-stage NSCLC and triple-negative breast cancer.
Neoadjuvant regimens typically involve anti–PD-1, anti–PD-L1, or anti–CTLA-4 antibodies, either as monotherapy or in combination with chemotherapy, administered over a defined period (often 2–4 cycles) before surgery.
Pathologic response to neoadjuvant immunotherapy is increasingly recognized as a surrogate marker for long-term benefit.
Ongoing trials continue to refine patient selection, optimal regimens, and the integration of neoadjuvant immunotherapy into multidisciplinary cancer care.