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Immunotherapy has revolutionized cancer treatment, however only a fraction of patients respond to treatment. Administering immunotherapy in the neo-adjuvant, pre-operative setting is an emerging therapeutic option and neoadjuvant immunotherapy–based clinical trials have now been conducted in several cancer types.
With this Collection, a partnership between Nature, Nature Medicine and Nature Communications, we welcome submissions of primary research papers that focus on neo-adjuvant immunotherapies and related combinatorial approaches (such as radio-immunotherapy or chemo-immunotherapy). Our interest is not limited to studies first reporting primary and secondary outcomes of interventional clinical trials, but we also encourage the submission of post hoc analyses of published neo-adjuvant immunotherapy trials. Associated studies using cancer patient samples, aiming to provide immunological mechanistic insights or to develop prognostic biomarkers, are also welcomed.
Please note that the journals follow the recommendations from the International Committee of Medical Journal Editors (ICMJE) and the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network for registration and reporting clinical studies. When preparing your submission, please refer to the shared journal guidelines.
We also remain interested in preclinical studies testing different neoadjuvant immunotherapy approaches. In particular, we encourage submissions of pre-clinical works assessing combinatorial approaches in a neo-adjuvant setting.
We will highlight relevant papers in this collection, together with neo-adjuvant immunotherapy-related articles recently published by the journals.
Patients with resectable clinical stage III or oligometastatic stage IV melanoma were given neoadjuvant relatlimab and nivolumab combination immunotherapy, which induced a high pathologic complete response rate, indicating the efficacy and safety of this regimen.
Imaging mass cytometry is used to map the multicellular dynamics of immune checkpoint blockade-treated triple-negative breast cancer, finding that key proliferative fractions and cell–cell interactions drive response, and immunotherapy distinctively remodels tumour structure.
In a randomized phase 3 trial, neoadjuvant anti-PD-1 plus either paclitaxel and cisplatin or nab-paclitaxel and cisplatin elicited a significantly superior pathological complete response rate versus neoadjuvant paclitaxel and cisplatin alone in patients with resectable locally advanced esophageal squamous cell carcinoma.
In a phase Ib trial, neoadjuvant nivolumab or nivolumab/relatlimab prior to chemoradiotherapy were well tolerated and liquid biopsy analyses show that undetectable ctDNA was associated with longer survival.
A neoadjuvant treatment regimen of anti-PD-L1 monotherapy followed by anti-PD-L1 plus chemotherapy was well tolerated and led to a major pathologic response rate of 70% in patients with resectable gastric or gastroesophageal junction adenocarcinoma.
In the phase 2 trial NEOSUMMIT-01, perioperative treatment of patients with locally advanced gastric or gastro-esophageal junction adenocarcinoma with anti-PD-1 and SOX/XELOX versus SOX/XELOX alone improved pathological complete response or near-complete response rate.
In a post hoc analysis of the phase 2 PRADO trial, baseline emotional distress was associated with reduced clinical responses in patients with stage III melanoma treated with neoadjuvant ipilimumab and nivolumab.
Analysis of the phase 3 CheckMate 816 trial shows that the depth of pathologic response as assessed by percent residual viable tumor is correlated with event-free survival following neoadjuvant immunotherapy plus chemotherapy, supporting pathologic response as a biomarker of survival.
In a phase 2 trial, the combination of gemcitabine, cisplatin and anti-PD-1 led to a clinical complete response in 43% of patients with muscle-invasive bladder cancer, which facilitated bladder sparing and was associated with long-term bladder-intact metastasis-free survival.
Individuals with cutaneous melanoma who are treated with neoadjuvant immunotherapy show a substantial improvement; this should be incorporated into standard care.
In the NATION-1907 trial, treatment of patients with resectable esophageal squamous cell carcinoma with the anti-PD-L1 agent adebrelimab was safe and showed preliminary overall survival efficacy, with responders exhibiting an immune-enriched tumor microenvironment phenotype at baseline.
Response to anti-PD-1 in patients with hepatocellular carcinoma is associated with clonal expansion of intratumoral CXCL13+ CD4+ helper T cells and effector-like CD8+ T cells, and local dendritic cells enriched in expression of maturation and regulatory molecules help facilitate CD8+ T cell differentiation.
The combination of neoadjuvant nivolumab, ipilimumab and chemotherapy showed promising efficacy in patients with resectable non-small cell lung cancer, with higher tumor immune cell infiltration and tertiary lymphoid structures after treatment compared with neoadjuvant nivolumab plus chemotherapy.
In a single-arm phase 2 study, enoblituzumab (a humanized, Fc-engineered, B7-H3-targeting antibody) was found to be safe and showed preliminary evidence of potential clinical activity in men with high-risk localized prostate cancer.
In a single-arm, non-randomized trial, neoadjuvant atezolizumab therapy in a large cohort of patients with resectable non-small cell lung cancer was safe and the study met its primary end point of major pathological response ≥15%.
Results from the PRADO extension cohort of the OpACIN-neo trial show that pathologic response rate to neoadjuvant ipilimumab and nivolumab can be used as a criterion for personalization of further treatment in stage III nodal melanoma, with the potential to reduce treatment morbidity and increase patient quality of life.
Neoadjuvant combination of immune checkpoint therapy in patients with cisplatin-ineligible bladder cancer achieves clinical efficacy and uncovers immune features as potential predictive biomarkers of treatment response.
Neoadjuvant immunotherapy combination in the NABUCCO trial elicits high pathological complete response rates in patients with locoregionally advanced (stage III) urothelial cancer and provides molecular biomarkers of treatment efficacy.
Results from the NICHE study show remarkable pathological responses to neoadjuvant combination immunotherapy in patients with early-stage colon cancer and uncover potential biomarkers of response.
Neoadjuvant PD-1 blockade in patients with resectable melanoma followed by adjuvant maintenance results in early immunological effects driving clinical benefit and reveals transcriptional and genomic mechanisms of response.
Neoadjuvant nivolumab treatment in patients with glioblastoma induces intratumoral immune activation and underscores the need for rationale-based combination approaches for improving clinical responses.
Immune checkpoint blockade could improve the complete cytoreduction rate with standard-of-care neoadjuvant chemotherapy (NACT) in patients with ovarian cancer. Here the authors report the results of a randomized phase II trial of NACT alone or in combination with pembrolizumab (anti-PD1) in patients with advanced high-grade serous carcinoma.
In the phase 2 study LCCC1520 (NCT02690558), clinical activity of pembrolizumab in combination with gemcitabine and cisplatin as neoadjuvant therapy in patients with muscle-invasive bladder cancer has been reported. Here the authors present molecular and immune cellular features associated with response to neoadjuvant chemo-immunotherapy.
The feasibility and efficacy of neoadjuvant immunotherapy for resectable hepatocellular carcinoma (HCC) have been previously suggested. Here the authors report the results of a phase 1b trial of neoadjuvant tislelizumab plus stereotactic body radiotherapy and adjuvant tislelizumab in early-stage resectable HCC.
Spatial positioning of cells within the tumour microenvironment may have a function in the success of immune checkpoint immunotherapy (ICI). Here the authors analyse spatial relationships from immunohistochemistry samples prior to ICI therapy and show that CD8 T cell or macrophage proximity to cancer cells is associated with better responses.
The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Here the authors report the results of a phase II clinical trial of camrelizumab (anti-PD1) and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma.
Neoadjuvant chemo-immunotherapy represents a therapeutic option for resectable head and neck squamous cell carcinoma (HNSCC). Here the authors report the results of a phase II trial of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced HNSCC.
Immunotherapy with immune checkpoint inhibitors and targeted therapy with BRAF and MEK inhibition have revolutionized the treatment of melanoma. Here the authors report the results of a phase II trial of neoadjuvant cobimetinib (MEK inhibitor) and atezolizumab (anti-PD-L1) with or without the BRAF inhibitor vemurafenib in patients with resectable Stage III melanoma.
Neoadjuvant treatment represents a therapeutic option for locally advanced gastric cancer (LAGC). Here the authors report the results of a randomized phase 2 trial of camrelizumab (anti-PD1) and apatinib (anti-VEGFR2) combined with nab-paclitaxel plus S-1 versus chemotherapy alone as neoadjuvant treatment for LAGC.
The authors previously reported the primary outcomes of a randomized phase II trial comparing neoadjuvant durvalumab (anti-PD-L1) alone or in combination with stereotactic radiotherapy in patients with early-stage NSCLC. Here, the authors report the secondary outcomes of the trial and post hoc analysis.
Recent evidence suggests the feasibility of neoadjuvant immune checkpoint inhibitors plus chemotherapy-based therapy for patients with early triple-negative breast cancer (TNBC). Here the authors report the results of a single-arm phase II trial of neoadjuvant camrelizumab (anti-PD-1) plus nab-paclitaxel and epirubicin for early TNBC.
Neoadjuvant chemotherapy followed by gastrectomy is considered standard of care for locally advanced gastric and gastroesophageal junction (G/GEJ) cancers. Here the authors report the results of a phase 2 trial of neoadjuvant sintilimab (anti-PD1) plus chemoradiotherapy in patients with locally advanced G/GEJ tumors.
GM-CSF-secreting whole-cell cancer vaccine (GVAX) promotes T-cell response against a range of tumor associated antigens in patients with pancreatic adenocarcinoma (PDA). Here the authors report the results of the initial three treatment arms of a platform trial of neoadjuvant and adjuvant GVAX alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable PDA.
In patients with locally advanced clear cell renal cell carcinoma (ccRCC), neoadjuvant therapy prior to curative nephrectomy has been shown to improve patient outcomes. Here, the authors report the safety and radiological efficacy of a phase II clinical trial investigating neoadjuvant sitravatinib (tyrosine kinase inhibitor) and nivolumab (PD-1 inhibitor) in locally advanced ccRCC.
Immune checkpoint inhibitors and antiangiogenic agents have shown some activity in patients with late-stage gastric cancer. Here the authors report the results of a phase II trial of neoadjuvant anti-PD1 (camrelizumab), antiangiogenic agent (apatinib), and chemotherapy (S-1 ± Oxaliplatin) in stage T4a/bN + M0 gastric cancer patients.
Surgery is an important part of treatment for gastric adenocarcinoma, however, the consensus on perioperative care is less clear. Here, the authors report the results of a phase II clinical trial investigating neoadjuvant camrelizumab with concurrent chemoradiotherapy, followed by surgery for the treatment of advanced gastric adenocarcinoma.
In patients with locally advanced resectable oral squamous cell carcinoma (OSCC), the risk of recurrence and metastasis following treatment is high. Here, a phase I clinical trial reports safety and pathological response of neoadjuvant camrelizumab and apatinib in patients with locally advanced resectable OSCC.
Immune checkpoint blockade has become standard care for patients with recurrent metastatic head and neck squamous cell carcinoma (HNSCC). Here the authors present the results of a non-randomized phase Ib/IIa trial, reporting safety and efficacy of neoadjuvant nivolumab monotherapy and nivolumab plus ipilimumab prior to standard-of-care surgery in patients with HNSCC. .
Different neoadjuvant therapies have been proposed to improve immunotherapy for cancer treatment. Here, the authors perform a phase Ib clinical trial where an agonist OX40 antibody provided prior to surgery is well tolerated and increases proliferation and activation of tumor antigen-specific T cells in head and neck cancer patients.