Nature Medicine, Год журнала: 2024, Номер 30(11), С. 3223 - 3235
Опубликована: Сен. 16, 2024
Immune checkpoint inhibition (ICI) with chemotherapy is now the standard of care for stage II-III triple-negative breast cancer; however, it largely unknown which patients ICI without could be an option and what benefit combination be. The adaptive BELLINI trial explored whether short induces immune activation (primary end point, twofold increase in CD8
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Авг. 28, 2023
Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel LAG-3 drugs have also been approved clinical application. With the widespread use of drug, we must deeply analyze dilemma agents seek a breakthrough treatment prospect. Over past decades, these demonstrated dramatic efficacy, especially patients with melanoma non-small cell lung cancer (NSCLC). Nonetheless, field broad concept solid tumours, non-specific indications, inseparable immune response side effects, unconfirmed progressive disease, complex regulatory networks resistance are four barriers that limit its Fortunately, successful trials ICB combination therapies, advent era oncolytic virus gene editing, technical mRNA vaccines nano-delivery systems made remarkable breakthroughs currently. In this review, enumerate mechanisms each checkpoint targets, associations between tumour mutation burden, key or signalling pathways, specific evidence efficacy classical targets new among different types put forward dialectical thoughts on drug safety. Finally, discuss importance accurate triage based recent advances predictive biomarkers diagnostic testing techniques.
Язык: Английский
Процитировано
239
Nature, Год журнала: 2022, Номер 611(7934), С. 155 - 160
Опубликована: Окт. 26, 2022
Abstract Relatlimab and nivolumab combination immunotherapy improves progression-free survival over monotherapy in patients with unresectable advanced melanoma 1 . We investigated this regimen resectable clinical stage III or oligometastatic IV (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg relatlimab 160 intravenously every 4 weeks) followed by surgery, then ten of adjuvant therapy. The primary end point was pathologic complete response (pCR) rate 2 resulted 57% pCR 70% overall among 30 treated. radiographic using Response Evaluation Criteria Solid Tumors 1.1 57%. No grade 3–4 immune-related adverse events were observed the setting. 1- 2-year recurrence-free 100% 92% for any response, compared to 88% 55% who did not have a ( P = 0.005). Increased immune cell infiltration at baseline, decrease M2 macrophages during treatment, associated response. Our results indicate that induces high rate. Safety therapy is favourable other regimens. These data, RELATIVITY-047 trial , provide further confirmation efficacy safety new regimen.
Язык: Английский
Процитировано
223
Drugs, Год журнала: 2023, Номер 83(3), С. 217 - 248
Опубликована: Янв. 16, 2023
Язык: Английский
Процитировано
115
Immunity, Год журнала: 2023, Номер 56(10), С. 2254 - 2269
Опубликована: Сен. 11, 2023
Язык: Английский
Процитировано
114
Critical Reviews in Oncology/Hematology, Год журнала: 2022, Номер 174, С. 103679 - 103679
Опубликована: Апрель 6, 2022
Immunotherapy has changed the treatment landscape of Head and Neck cancer (HNC). Different immune checkpoint inhibitors targeting PD-1/PD-L1 axis have been approved for different disease settings many others, alone or in combination, are currently under investigation. Otherwise, as other types, efficacy, resistance mechanisms, not clearly understood. Considering heterogeneity benefit reported clinical trials, cost-efficacy analysis development an effective patient selection encouraged. pathways involving innate immunity, regulatory T lymphocytes microbiome emerging new potential biomarkers, supported by preclinical translational data. In this review we report current evidence on immunotherapy HNC with updates from main 2021 oncology events ASCO, AACR ESMO meetings. We focus trials results single agent combination scenario, (neo)adjuvant to metastatic setting, describing also novel about efficacy biomarkers.
Язык: Английский
Процитировано
74
Nature Communications, Год журнала: 2022, Номер 13(1)
Опубликована: Сен. 14, 2022
Abstract Novel neoadjuvant therapy regimens are warranted for oral squamous cell carcinoma (OSCC). In this phase I trial (NCT04393506), 20 patients with locally advanced resectable OSCC receive three cycles of camrelizumab (200 mg, q2w) and apatinib (250 once daily) before surgery. The primary endpoints safety major pathological response (MPR, defined as ≤10% residual viable tumour cells). Secondary include 2-year survival rate local recurrence (not reported due to inadequate follow-up). Exploratory the relationships between PD-L1 combined positive score (CPS, number PD-L1-stained cells divided by total cells, multiplied 100) other immunological genomic biomarkers response. Neoadjuvant treatment is well-tolerated, MPR 40% (8/20), meeting endpoint. All five CPS ˃10 achieve MPR. Post-hoc analysis show 18-month locoregional rates 10.5% (95% CI: 0%–24.3%) 95% 85.4%–100.0%), respectively. Patients achieving more CD4+ T-cell infiltration than those without (P = 0.02), decreased CD31 ɑ-SMA expression levels observed after therapy. conclusion, safe yields a promising OSCC.
Язык: Английский
Процитировано
73
Nature Medicine, Год журнала: 2023, Номер 30(1), С. 218 - 228
Опубликована: Окт. 30, 2023
Abstract Neoadjuvant immunotherapy plus chemotherapy improves event-free survival (EFS) and pathologic complete response (0% residual viable tumor (RVT) in primary (PT) lymph nodes (LNs)), is approved for treatment of resectable lung cancer. Pathologic assessment after neoadjuvant therapy the potential analog to radiographic advanced disease. However, %RVT thresholds beyond major (≤10% RVT) have not been explored. was prospectively assessed randomized, phase 3 CheckMate 816 trial (NCT02998528), which evaluated nivolumab (anti-programmed death protein 1) patients with RVT, regression necrosis were quantified (0–100%) PT LNs using a pan-tumor scoring system tested association EFS prespecified exploratory analysis. Regardless LN involvement, improved 0% versus >0% RVT-PT (hazard ratio = 0.18). predicted (area under curve 0.74); 2-year rates 90%, 60%, 57% 39% 0–5%, >5–30%, >30–80% >80% respectively. Each 1% RVT associated 0.017 hazard increase EFS. Combining from helped differentiate outcomes. When compared circulating DNA clearance, best approximated These findings support as an emerging surrogate. Further full spectrum cancer other types warranted. ClinicalTrials.gov registration: NCT02998528 .
Язык: Английский
Процитировано
73
Annals of Oncology, Год журнала: 2023, Номер 34(4), С. 420 - 430
Опубликована: Янв. 18, 2023
Язык: Английский
Процитировано
71
Cell, Год журнала: 2024, Номер 187(9), С. 2324 - 2335.e19
Опубликована: Апрель 1, 2024
Microbial communities are resident to multiple niches of the human body and important modulators host immune system responses anticancer therapies. Recent studies have shown that complex microbial present within primary tumors. To investigate presence relevance microbiome in metastases, we integrated mapping assembly-based metagenomics, genomics, transcriptomics, clinical data 4,160 metastatic tumor biopsies. We identified organ-specific tropisms microbes, enrichments anaerobic bacteria hypoxic tumors, associations between diversity tumor-infiltrating neutrophils, association Fusobacterium with resistance checkpoint blockade (ICB) lung cancer. Furthermore, longitudinal sampling revealed temporal evolution depleted upon ICB. Together, generated a pan-cancer resource may contribute advancing treatment strategies.
Язык: Английский
Процитировано
52
Nature reviews. Cancer, Год журнала: 2024, Номер 24(6), С. 399 - 426
Опубликована: Май 13, 2024
Язык: Английский
Процитировано
47