Comparison of immunotherapy based total neoadjuvant therapy or standard neoadjuvant chemoradiation for locally advanced rectal cancer: a multi-institutional retrospective study DOI Creative Commons
Zhao Wen, Wenxing Gao,

Jitao Du

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 14, 2025

Background Combining radiation therapy with immunotherapy produces a synergistic effect in patients microsatellite stable/mismatch repair-proficient (MSS/pMMR) locally advanced rectal cancer (LARC). This study aimed to evaluate the long-term outcomes and safety of combined long-course chemoradiotherapy (ICIs + nCRT) versus total neoadjuvant TNT). Methods retrospective collected clinical data adult T3-4 and/or N1 adenocarcinoma who underwent ICIs TNT or nCRT followed by curative surgery at four medical centers between March 2020 August 2021. The compared efficacy, disease-free survival (DFS), overall (OS) 3 years postoperatively, adverse event. Results Among 211 enrolled patients, 89 (42%) received TNT, while 122 (58%) nCRT, median age 56.0 (range, 20.0-75.0 years). group had higher number resected lymph nodes (15.0 [range, 4.0-37.0] vs. 13.0 3.0-33.0], P =0.028) ICIs+nCRT group. However, groups no substantial difference operative time. pathological complete response (pCR) rate was 49.4% (44/89, 95% confidence interval [CI] 39.8%-61.3%) 35.3% (43/122, CI 26.8%-44.4%) group, respectively, significant ( =0.039). After adjusting for potential confounders, 3-year DFS rates were comparable two (84.3% 81.9%; =0.620), as OS (94.0% 91.1%; =0.634). Factors independently associated poorer included ≤50 =0.044) (NAR) score ≥8 =0.008). Similarly, aged =0.025) exhibited trend toward worse than those older 50 years. profiles treatment similar. Conclusions Overall, demonstrated therapeutic efficacy profile LARC MSS/pMMR status. Although achieved numerically downstaging rates, it not improved outcomes. These findings underscore importance refining patient selection criteria making judicious decisions enhance prognosis individuals cancer.

Язык: Английский

Exosomal circular RNAs: A chief culprit in cancer chemotherapy resistance DOI
Xu Guo,

Congying Gao,

Dong‐Hua Yang

и другие.

Drug Resistance Updates, Год журнала: 2023, Номер 67, С. 100937 - 100937

Опубликована: Фев. 2, 2023

Язык: Английский

Процитировано

100
Advances of Wnt Signalling Pathway in Colorectal Cancer DOI Creative Commons

Yaoyao Zhu,

Xia Li

Cells, Год журнала: 2023, Номер 12(3), С. 447 - 447

Опубликована: Янв. 30, 2023

Colorectal cancer (CRC) represents one of the most common cancers worldwide, with a high mortality rate despite decreasing incidence and new diagnostic therapeutic strategies. CRC arises from both epidemiologic molecular backgrounds. In addition to hereditary factor genetic mutations, strongly varying is closely linked chronic inflammatory disorders intestine terrible dietary habits. The Wnt signalling pathway complex regulatory network that implicated in many physiological processes, including occurrence, development, prognosis, invasion, metastasis. It currently believed include classical Wnt/β-catenin, Wnt/PCP, Wnt/Ca2+. this review, we summarise recent mechanisms potential regulators three branches CRC.

Язык: Английский

Процитировано

54
The opportunities and challenges in immunotherapy: Insights from the regulation of PD-L1 in cancer cells DOI Creative Commons
Qingyu Lin, Xingwen Wang, Ying Hu

и другие.

Cancer Letters, Год журнала: 2023, Номер 569, С. 216318 - 216318

Опубликована: Июль 15, 2023

The immunosuppressive molecule programmed death-ligand 1 (PD-L1) is frequently upregulated in human cancers. Binding of PD-L1 to its receptor, death-1 (PD-1), on activated T cells facilitates cancer evade the host immune system. Antibody-based PD-1/PD-L1 inhibitors can inhibit interaction allowing reactivate cytotoxic eradicate advanced cells. However, majority patients fail respond anti-PD-1/PD-L1 therapies and molecular mechanisms for this remain poorly understood. Recent studies show that expression level tumor affect clinical efficacy checkpoint therapies. Thus, furthering our understanding regulatory will be critical improve response rates Here we review recent studies, primarily focusing regulate at transcriptional, post-transcriptional protein level, with purpose drive development more targeted effective

Язык: Английский

Процитировано

50
Recent developments in immunotherapy for gastrointestinal tract cancers DOI Creative Commons

Xiaoyi Chong,

Yelizhati Madeti,

Jieyuan Cai

и другие.

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Авг. 9, 2024

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. role immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in treatment advanced perioperative GI Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen unselected gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), esophageal (EC). In addition, encouraging performance claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy later-line cancers brings new hope cell solid tumour treatment. Nevertheless, remains yet precise, researchers are dedicated to further maximising optimising efficacy. This review summarises important research, latest progress, future directions including EC, G/GEJC, CRC.

Язык: Английский

Процитировано

17
New insight in immunotherapy and combine therapy in colorectal cancer DOI Creative Commons
Kai Ji,

Hang Jia,

Zixuan Liu

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Янв. 7, 2025

The advent of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) treatment marks a major breakthrough. These therapies have proven safer and more effective than traditional radiotherapy targeted treatments. Immunotherapies like pembrolizumab, nivolumab, ipilimumab pioneered new avenues, potentially improving patient outcomes quality life. Additionally, advances immunotherapy prompted detailed research into CRC therapies, especially those integrating ICIs with conventional treatments, providing hope for patients shaping future practice. This review delves the mechanisms various evaluates their therapeutic potential when combined radiotherapy, chemotherapy, clinical settings. It also sheds light on current application involving treatment.

Язык: Английский

Процитировано

2
Target delivery of a PD-1-TREM2 scFv by CAR-T cells enhances anti-tumor efficacy in colorectal cancer DOI Creative Commons
Jian Chen, Tianchuan Zhu, Guanmin Jiang

и другие.

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Авг. 10, 2023

Abstract Background Chimeric antigen receptor (CAR) -T cell therapy is an efficient therapeutic strategy for specific hematologic malignancies. However, positive outcomes of this novel in treating solid tumors are curtailed by the immunosuppressive tumor microenvironment (TME), wherein signaling checkpoint programmed death-1 (PD-1)/PD-L1 directly inhibits T-cell responses. Although checkpoint-targeted immunotherapy succeeds increasing number T cells produced to control growth, desired effect mitigated action myeloid-derived suppressor (MDSCs) and tumor-associated macrophages (TAMs) TME. Previous studies have confirmed that targeting triggering-receptor-expressed on myeloid 2 (TREM2) TAMs MDSCs enhances anti-PD-1 immunotherapy. Methods We constructed carcinoembryonic (CEA)-specific CAR-T colorectal cancer (CRC)-specific antigens with autocrine PD-1-TREM2 single-chain variable fragment (scFv) target PD-1/PD-L1 pathway, TAMs. Results found PD-1-TREM2-targeting scFv inhibited activation pathway. In addition, these secreted scFvs blocked binding ligands TREM2 receptors present TAMs, reduced proportion enhanced effector function, thereby mitigating immune resistance scFv-secreting resulted highly effective elimination compared achieved PD-1 a subcutaneous CRC mouse model. Moreover, remained localized within exhibited extended half-life. Conclusions Together, results indicate strong potential as CRC.

Язык: Английский

Процитировано

37
Theranostics Nanomedicine Applications for Colorectal Cancer and Metastasis: Recent Advances DOI Open Access

Phanindra Babu Kasi,

Venkata Ramana Mallela, Filip Ambrożkiewicz

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 7922 - 7922

Опубликована: Апрель 27, 2023

Colorectal cancer (CRC) is the third most common worldwide, and metastatic CRC a fatal disease. The CRC-affected tissues show several molecular markers that could be used as fresh strategy to create newer methods of treating condition. liver peritoneum are where metastasis occurs frequently. Once tumor has metastasized liver, peritoneal carcinomatosis frequently regarded disease's final stage. However, nearly 50% patients with do not have metastases. New diagnostic therapeutic approaches must developed due poor response present treatment choices in advanced stages necessity an accurate diagnosis early stages. Many unique amazing nanomaterials promise for both may found nanotechnology. Numerous nanoformulations, including carbon nanotubes, dendrimers, liposomes, silica nanoparticles, gold metal-organic frameworks, core-shell polymeric nano-formulations, nano-emulsion systems, among others, can targeted anticancer drug delivery purposes CRC. Theranostic combined nanomedicine been proposed revolutionary approach improve detection treatment. This review highlights recent studies, potential, challenges development nanoplatforms

Язык: Английский

Процитировано

24
XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial DOI Creative Commons

Qiuzhong Pan,

Jingjing Zhao, Liang Liu

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Апрель 2, 2024

Abstract Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed efficacy and adverse events (AEs) of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX bevacizumab as a first-line in patients mCRC. A total 202 participants were enrolled randomly assigned 1:1 ratio to receive either (the control group, n = 102) or same regimen autologous PD1-T cell immunotherapy 100) every 21 days up 6 cycles, followed by maintenance capecitabine bevacizumab. The main endpoint was progression-free survival (PFS). median follow-up 19.5 months. Median PFS 14.8 months (95% CI, 11.6–18.0) group compared 9.9 (8.0–11.8) (hazard [HR], 0.60 [95% 0.40–0.88]; p 0.009). overall (OS) not reached 25.6 18.3–32.8) (HR, 0.57 0.33–0.98]; 0.043). Grade higher AEs occurred 20.0% 23.5% groups, no toxicity-associated deaths reported. addition demonstrates significant clinical improvement OS well tolerability previously untreated

Язык: Английский

Процитировано

12
FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer DOI Creative Commons

Haiyang Li,

Na Zheng,

Anning Guo

и другие.

Cell Death and Disease, Год журнала: 2024, Номер 15(2)

Опубликована: Фев. 1, 2024

Abstract Programmed cell death 1 ligand (PDL1)/programmed (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on effectiveness are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed malignant cells CRC microenvironment, notably, expression level was related to tumor immune evasion and clinical efficacy anti-PD1 therapy. Further studies determined hypoxic microenvironment induced via HIF1α cells, bind transcription factor c-Myc (354–406 amino acids) suppress latter’s ubiquitination increase its stability, thereby up-regulated PDL1 indoleamine 2,3-dioxygenase (IDO1). The results immunocompetent models verified FSLT3 knockout increased proportion CD8 + T reduced regulatory (CD25 Foxp3 ) exhausted (PD1 ), synergistically improved therapy efficacy. To sum up, enhanced c-Myc-mediated transcriptional regulation promote attenuates CRC, suggesting potential as biomarker immunotherapeutic well novel target CRC.

Язык: Английский

Процитировано

9
Unveiling intratumoral microbiota: An emerging force for colorectal cancer diagnosis and therapy DOI Creative Commons

Jinjing Zhang,

Penghui Wang, Jiafeng Wang

и другие.

Pharmacological Research, Год журнала: 2024, Номер 203, С. 107185 - 107185

Опубликована: Апрель 12, 2024

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body contribute significantly to both physiological pathological processes. Nowadays, development sequencing technology has revealed presence composition intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, Bacteroides, shed light on significant involvement progression colorectal cancer (CRC). Here, we summarized current understanding microbiota CRC outline potential translational clinical applications diagnosis, prevention, treatment CRC. We focused reviewing microbial therapies targeting improve efficacy safety chemotherapy immunotherapy for identify biomarkers diagnosis prognosis Finally, emphasized obstacles solutions translating knowledge into practice.

Язык: Английский

Процитировано

8