Primary Colorectal Cancer Research Articles

(Pro)renin receptor promotes colorectal cancer progression through inhibiting the NEDD4L-mediated Wnt3 ubiquitination and modulating gut microbiota

BackgroundWe previously found that (pro)renin receptor ((P)RR) augments Wnt3 protein without affecting Wnt3 gene transcription in colorectal cancer (CRC) cells, thus contributes to CRC initiation. The present study aims to investigate whether (P)RR further promotes CRC progression following oncogenesis and the related mechanisms. Notably, we deeply elaborate how (P)RR affects Wnt3 protein level and the key enzyme that mediates this process.MethodsImmunohistochemistry, western blotting and immunofluorescence were performed to detect protein expression status. A kind of gastrointestinal epithelium-specific ATP6AP2 ((P)RR encoding gene) knock-in mice were generated using Crispr/Cas9 system.ResultsWe found that increased (P)RR expression in primary CRC lesions is positively associated with higher Wnt3 protein level and disease progression. Progressive CRC presents less colocalization of Wnt3 and an E3 ubiquitin ligase NEDD4L in primary lesions than non-progressive CRC. In colon cancer cells, (P)RR dramatically inhibits the NEDD4L-mediated Wnt3 protein ubiquitination. ATP6AP2 knock-in mice show more diminished Wnt3-NEDD4L colocalization in their gut epithelium in comparison to wildtype mice. They also have abnormal gut bacterial flora distribution. Especially, Lachnospiraceae_NK4A136 and Bacteroides genus, which are generally protective against CRC, are suppressed in guts of ATP6AP2 knock-in mice.ConclusionsCollectively, (P)RR promotes CRC progression through inhibiting the NEDD4L-mediated Wnt3 ubiquitination and modulating gut microbiota.5Fh7m3ebJHKpa3LjUnmMxGVideo

Single-Exosome Profiling Identifies ITGB3+ and ITGAM+ Exosome Subpopulations as Promising Early Diagnostic Biomarkers and Therapeutic Targets for Colorectal Cancer.

Tumor metastasis is a hallmark of colorectal cancer (CRC), in which exosome plays a crucial role with its function in intercellular communication. Plasma exosomes were collected from healthy control (HC) donors, localized primary CRC and liver-metastatic CRC patients. We performed proximity barcoding assay (PBA) for single-exosome analysis, which enabled us to identify the alteration in exosome subpopulations associated with CRC progression. By in vitro and in vivo experiments, the biological impact of these subpopulations on cancer proliferation, migration, invasion, and metastasis was investigated. The potential application of exosomes as diagnostic biomarkers was evaluated in 2 independent validation cohorts by PBA. Twelve distinct exosome subpopulations were determined. We found 2 distinctly abundant subpopulations: one ITGB3-positive and the other ITGAM-positive. The ITGB3-positive cluster is rich in liver-metastatic CRC, compared to both HC group and primary CRC group. On the contrary, ITGAM-positive exosomes show a large-scale increase in plasma of HC group, compared to both primary CRC and metastatic CRC groups. Notably, both discovery cohort and validation cohort verified ITGB3+ exosomes as potential diagnostic biomarker. ITGB3+ exosomes promote proliferation, migration, and invasion capability of CRC. In contrast, ITGAM+ exosomes suppress CRC development. Moreover, we also provide evidence that one of the sources of ITGAM+ exosomes is macrophage. ITGB3+ exosomes and ITGAM+ exosomes are proven 2 potential diagnostic, prognostic, and therapeutic biomarkers for management of CRC.

Percutaneous Image-Guided Cryoablation of Metastatic Colorectal Adenocarcinoma to the Abdominal Wall

AbstractAbdominal wall metastases are rarely seen in primary colorectal cancer; the majority of cases are attributed to seeding from previous procedures. We report a case of percutaneous cryoablation of metastatic colorectal cancer to the abdominal wall with no evidence of recurrence 1 year later.

A clinicopathological study of the correlation of level of carcinoembryonic antigen in colorectal carcinoma in a tertiary care medical college in Eastern India

Background: For different cancers, different tumor markers are overexpressed. Carcinoembryonic antigen (CEA) levels are raised commonly in adenocarcinoma of colon, breast, and lung. About 80% of primary colorectal cancers (CRCs) show high serum CEA levels. Hence, CEA levels can be used as a prognostic factor - for both metastasis and recurrence - with persistent high levels. Currently, the American Society of Clinical Oncology recommends CEA as tumor marker and prognostic indicator in CRC patients. Aim and Objectives: The aim of the study was to determine the high level of CEA in CRCs and to study the level of CEA in cases of metastases and recurrence and to determine the sensitivity of CEA value in prognosis of CRCs. Materials and Methods: It was a prospective observational study. All the patients more than 20 years of age and of both sexes were included in this study who were diagnosed with primary localized CRC, metastatic CRC, or recurrent disease. The study was performed in the Department of General Surgery, R. G. Kar Medical College and Hospital between January 2020 and August 2021. Results: Total cases were classified according to Duke staging - 10% in Group A, 19% in Group B, 38% in Group C, and 33% in Group D. In Group A and B, about 35% of patients had increased CEA levels, whereas in Group C and D, more than 90% of patients had increased CEA levels with significant P < 0.05. Overall 80% of the patients had elevated CEA levels, so remaining 20% had normal values. In cases of recurrent colorectal carcinoma, >90% of patients had raised CEA levels, and in metastatic disease cases, CEA level was significantly raised in 82% of patients. Conclusion: In case of colorectal CA, preoperative raised serum CEA level is associated with poor prognosis, as chance of recurrence increased. Along with that increased CEA level is also associated with increased chance of metastatic disease. Hence, serial monitoring of serum CEA level in postoperative period may help to detect any recurrence early, thus reducing chance of mortality and morbidity.

Integrated proteomic and phosphoproteomic data-independent acquisition data evaluate the personalized drug responses of primary and metastatic tumors in colorectal cancer.

Mass spectrometry (MS)-based proteomics and phosphoproteomics are powerful methods to study the biological mechanisms, diagnostic biomarkers, prognostic analysis, and drug therapy of tumors. Data-independent acquisition (DIA) mode is considered to perform better than data-dependent acquisition (DDA) mode in terms of quantitative reproducibility, specificity, accuracy, and identification of low-abundance proteins. Mini patient derived xenograft (MiniPDX) model is an effective model to assess the response to antineoplastic drugs in vivo and is helpful for the precise treatment of cancer patients. Kinases are favorable spots for tumor-targeted drugs, and their functional completion relies on signaling pathways through phosphorylating downstream substrates. Kinase-phosphorylation networks or edge interactions are considered more credible and permanent for characterizing complex diseases. Here, we provide a workflow for personalized drug response assessment in primary and metastatic colorectal cancer (CRC) tumors using DIA proteomic data, DIA phosphoproteomic data, and MiniPDX models. Three kinase inhibitors, afatinib, gefitinib, and regorafenib, are tested pharmacologically. The process mainly includes the following steps: clinical tissue collection, sample preparation, hybrid spectral libraries establishment, MS data acquisition, kinase-substrate network construction, in vivo drug test, and elastic regression modeling. Our protocol gives a more direct data basis for individual drug responses, and will improve the selection of treatment strategies for patients without the druggable mutation.

Indocyanine green in liver tumor resection

Primary liver cancer and colorectal cancer liver metastases are among the leading causes of cancer-related mortality worldwide. Surgery is one of the main methods of treatment to achieve the best results in overall and recurrence-free survival. The main objectives in this surgery are preoperative planning, assessment of functional viability of liver parenchyma and total resection with low complication rate. Post-resection liver failure is one of the most formidable and often fatal complication following functional failure of liver remnant. Thus, preoperative assessment of liver functional reserves is a necessary step for adequate selection of patients and safe surgery. Passive liver tests, such as biochemical parameters or clinical scales, do not accurately reflect the actual functional component of liver parenchyma. The most accurate method is dynamic quantitative test of liver, such as indocyanine green clearance. The authors discuss the practical aspects of preoperative assessment of liver functional reserves using indocyanine green, as well as the concept and technical foundations of fluorescent imaging in hepatobiliary surgery.

The influence of frailty on perioperative outcomes in patients undergoing surgical resection of liver metastases: a nationwide readmissions database study.

Liver metastases arise frequently from primary colorectal, pancreatic, and breast cancers. Research has highlighted the patient's frailty status as an important predictor of outcomes, but the literature evaluating the role of frailty in patients with secondary metastatic disease of the liver remains limited. Using predictive analytics, we evaluated the role of frailty in patients who underwent hepatectomy for liver metastases. We used the Nationwide Readmissions Database from 2016-2017 to identify patients who underwent resection of a secondary malignant neoplasm of the liver. Patient frailty was evaluated using the Johns Hopkins Adjusted Clinical Groups (JHACG) frailty-defining diagnosis indicator. Propensity score matching was performed and Mann-Whitney U testing was used to analyze complication rates. Receiver operating characteristic (ROC) curves were created following creation of logistic regression models for predicting discharge disposition. Frail patients reported significantly higher rates of nonroutine discharges, longer inpatient stays, greater costs, higher rates of acute infection, posthemorrhagic anemia, urinary tract infection (UTI), deep vein thrombosis (DVT), wound dehiscence and readmission, and greater mortality (P<0.05). Predictive models for patient discharge disposition, DVT and UTI demonstrated that the use of frailty status and age improved the area under the ROC curves significantly compared to models using age alone. Frailty was found to be significantly correlated with higher rates of medical complications during inpatient stay following hepatectomy in patients with liver metastasis. The inclusion of patient frailty status in predictive models improved their predictive capacity compared to those using age alone.

Spatial transcriptomics deconvolves prognosis in colorectal cancer with synchronous liver metastases

Background: Patients demonstrating strong immune responses to primary colorectal cancer (CRC) have a survival benefit following surgery, while those with predominantly stromal microenvironments do poorly. Biomarkers to identify patients with colorectal cancer liver metastases (CRLM) who have good prognosis following surgery for oligometastatic disease remain elusive. The aim of this study was to determine the practical application of a simple histological assessment of immune cell infiltration and stromal content in predicting outcome following synchronous resection of primary CRC and CRLM, and to interrogate the underlying functional biology that drives disease progression.

Simultaneous Laparoscopic Resection of Primary Colorectal Cancer and Synchronus Liver Metastases: Initial Experience of Single Institute

Simultaneous Laparoscopic Resection of Primary Colorectal Cancer and Synchronus Liver Metastases: Initial Experience of Single Institute

CD3+ and CD8+ T-Cell-Based Immune Cell Score and PD-(L)1 Expression in Pulmonary Metastases of Microsatellite Stable Colorectal Cancer

The objective of this study was to evaluate the prognostic value of CD3+ and CD8+ based immune cell score (ICS), programmed death -1 (PD-1) and programmed death ligand -1 (PD-L1) in pulmonary metastases of proficient mismatch repair colorectal cancer (CRC) patients. A total of 101 pulmonary metastases and 62 primary CRC tumours were stained for CD3+, CD8+, PD-1 and PD-L1 expression. The prognostic value of ICS, PD-1/PD-L1 expression in 67 first pulmonary metastases and 61 primary CRC tumour was analysed. Comparative analysis was also performed between primary tumours and pulmonary metastases, as well as between T-cell densities and PD-1/PD-L1 expression. The 5-year overall survival rates of low, intermediate, and high ICS in pulmonary metastases were 10.0%, 25.5% and 47.0% (p = 0.046), respectively. Patients with high vs. low ICS in pulmonary metastases had a significantly better 5-year survival (adjusted HR 0.25, 95% CI 0.09-0.75, p = 0.013). High tumour cell PD-L1 expression in the pulmonary metastases was associated with improved survival (p = 0.024). Primary tumour CD8+ expression was significantly correlated with all T-cell densities in pulmonary metastases. Conclusion: The ICS evaluated from the resected pulmonary metastases of CRC showed significant prognostic value. High PD-L1 expression in pulmonary metastases is associated with favourable prognosis.

Nutritional and functional status as indices of short- and long-term prognosis in patients undergoing surgery due to colorectal cancer

Introduction: Nutritional status and body composition parameters would seem to be reasonable prognostic factors in patients with colorectal cancer (CRC). The study aimed to investigate the relationships between numerous parameters of nutritional status and prognosis in patients undergoing surgery due to CRC. Material and methods: Clinical nutritional assessment and biochemical determinations were performed on 110 patients who underwent elective surgery due to primary CRC. Body composition was also analyzed using bioelectrical impedance (BIA) and computed tomography (CT) scans at the third lumbar (L3) vertebra using OsiriX software. Results: Patients who failed to attend a visit 3 months after surgery (n = 15; 13.6%) were more likely to be sarcopenic, with lower baseline functional status, handgrip strength, skeletal muscle (SM) parameters in BIA and a smaller SM area in CT. Compared to those who died during, on average, 3.6 years of follow-up (n = 33; 30%), patients who survived had, at baseline, a significantly higher Mini-Nutritional Assessment (MNA) score, lower waist-to-height ratio (WHtR), and higher scores on functional status scales. In a Cox’s proportional-hazards model, in addition to an advanced WHO CRC stage, scores for MNA (HR; 95% CI: 0.85; 0.74–0.98; p = 0.021), Patient-Generated Subjective Global Assessment (PG-SGA), instrumental activities of daily living (IADL), and WHtR (3.68; 1.03–13.13; p = 0.049) were independent risk factors for death. Conclusions: Patients’ functional status 3 months after surgery due to CRC was related to baseline SM strength, mass, and functional performance, whereas 3.5-year mortality was associated with lower MNA and IADL scores and higher WHtR and PG-SGA scores.

The sodium channel subunit SCNN1B suppresses colorectal cancer via suppression of active c-Raf and MAPK signaling cascade

The incidence of colorectal cancer (CRC) is rising worldwide. Here, we identified SCNN1B as an outlier down-regulated in CRC and it functions as a tumor suppressor. SCNN1B mRNA and protein expression were down-regulated in primary CRC and CRC cells. In a tissue microarray cohort (N = 153), SCNN1B protein was an independent prognostic factor for favorable outcomes in CRC. Ectopic expression of SCNN1B in CRC cell lines suppressed cell proliferation, induced apoptosis, and cell cycle arrest, and suppressed cell migration in vitro. Xenograft models validated tumor suppressive function of SCNN1B in vivo. Mechanistically, Gene Set Enrichment Analysis (GSEA) showed that SCNN1B correlates with KRAS signaling. Consistently, MAPK qPCR and kinase arrays revealed that SCNN1B suppressed MAPK signaling. In particular, SCNN1B overexpression suppressed p-MEK/p-ERK expression and SRE-mediated transcription activities, confirming blockade of Ras-Raf-MEK-ERK cascade. Mechanistically, SCNN1B did not affect KRAS activation, instead impairing activation of c-Raf by inducing its inhibitory phosphorylation and targeting active c-Raf for degradation. The ectopic expression of c-Raf fully rescued cell proliferation and colony formation in SCNN1B-overexpressing CRC cells, confirming c-Raf as the principal molecular target of SCNN1B. In summary, we identified SCNN1B as a tumor suppressor by functioning as a c-Raf antagonist, which in turn suppressed oncogenic MEK-ERK signaling.

Correlation of long interspersed element-1 open reading frame 1 and c-Met proto-oncogene protein expression in primary and recurrent colorectal cancers

Background: Colorectal cancer is one of the most common cancers worldwide. Colorectal cancer that has recurred and metastasized to other organs also has a very poor prognosis. According to recent studies, the long interspersed element-1 (LINE-1) retrotransposon open reading frame (ORF) is located in the intron of the c-Met proto-oncogene, which is involved in cancer progression and metastasis, and regulates its expression. However, no study has compared the expression patterns of LINE-1 ORF1 and c-Met, which are closely related to cancer progression and metastasis, and their correlation in primary and recurrent cancers.Methods: In the present study, we compared the expression patterns of LINE-1 ORF1 and c-Met in both primary and recurrent colorectal cancer tissues from 10 patients. Expression patterns and correlations between LINE-1 ORF1 and c-Met proto-oncogene proteins were analyzed by immunofluorescence staining using both LINE-1 ORF1 and c-Met antibodies.Results: The expression patterns of LINE-1 ORF1 and c-Met showed significant individual differences, and the expression of both proteins was correlated in all colorectal cancer patients. However, the expression levels of LINE-1 ORF1 and c-Met were not significantly different between primary and recurrent colorectal cancers. Conclusions: The protein expression levels of LINE-1 ORF1 and c-Met were correlated, but did not change significantly in cases of recurrent colorectal cancer in the same patient.

Biomarker concordance between primary colorectal cancer and ovarian metastases: a Dutch cohort study.

The genetic characteristics and mismatch repair (MMR) status of the primary tumor and corresponding metastases in colorectal cancer (CRC) are generally considered to be highly concordant. This implies that either the primary or metastatic tumor can be used for testing gene mutation and MMR status. However, whether this is also true for CRC and their ovarian metastases is currently unknown. Ovarian metastases generally show a poorer response to systemic therapy compared to other metastatic sites. Differences in biomarker status between primary CRC and ovarian metastases could possibly explain this difference in therapy response. The study cohort was selected from CRC patients treated in two Dutch hospitals. Eligible patients with CRC and ovarian metastasis who were surgically treated between 2011 and 2018 were included. CRC and corresponding ovarian metastatic tissues were paired. Gene mutation status was established using next-generation sequencing, while the MMR status was established using either immunohistochemistry or microsatellite instability analysis. Matched samples of CRC and ovarian metastasis from 26 patients were available for analysis. A biomarker concordance of 100% was detected. Complete biomarker concordance was found between MMR proficient CRC and their matching ovarian metastasis. Biomarker testing of MMR proficient CRC tissue appears to be sufficient, and additional testing of metastatic ovarian tissue is not necessary. Differences in therapy response between ovarian metastases and other metastases from CRC are thus unlikely to be caused by differences in the genetic status.

Preoperative Cancer Inflammation Prognostic Index as a Superior Predictor of Short- and Long-Term Outcomes in Patients with Stage I-III Colorectal Cancer after Curative Surgery.

Inflammatory reactions play a crucial role in cancer progression and may contribute to systemic inflammation. In routine clinical practice, some inflammatory biomarkers can be utilized as valuable predictors for colorectal cancer (CRC). This study aims to determine the usefulness of a novel cancer-inflammation prognostic index (CIPI) marker derived from calculating carcinoembryonic antigen (CEA) multiplied by the neutrophil-to-lymphocyte ratio (NLR) values established for non-metastatic CRCs. Between January 1995 and December 2018, 12,092 patients were diagnosed with stage I to III primary CRC and had radical resection-they were all included in this study for further investigation. There were 5996 (49.6%) patients in the low-CIPI group and 6096 (50.4%) patients in the high-CIPI group according to the cutoff value of 8. For long-term outcomes, the high-CIPI group had a significantly higher incidence of recurrence (30.6% vs. 16.0%, p &lt; 0.001) and worse relapse-free survival (RFS) and overall survival (OS) rates (p &lt; 0.001). High CIPI was an independent prognostic factor for RFS and OS in univariate and multivariate analyses. This research is the first to document the independent significance of CIPI as a prognostic factor for CRC. To ensure that it works, this CIPI needs to be tested on more CRC prediction models.

Heightened Procoagulation after Post-Operative Thromboprophylaxis Completion in Patients with Metastatic Bone Disease from Primary Colorectal Cancer.

Platelets play a role in venous thromboembolism (VTE) and in mediating colorectal cancer (CRC) progression. Still, platelets' role in hypercoagulability after surgical intervention for metastatic bone disease (MBD) is ill-defined. In this quantitative observational study, we utilized a high-resolution imaging approach to temporally examine platelet procoagulant membrane dynamics (PMD) in four patients with MBD from primary CRC (CRC/MBD), before and after surgical intervention, over a 6-month period. We coupled this investigation with thrombelastography, quantitative plasma shotgun proteomics, and biochemical analysis. The plasma of CRC/MBD patients was enriched in ADAM1a, ADAMTS7, and physiological ligands for platelet glycoprotein-VI/spleen tyrosine kinase (GPVI/Syk) activation. Thromboprophylaxis attenuated procoagulation upon its initial prescription (post-operative day one, POD1); however, all patients experienced rebound procoagulation between POD3 and POD14, which was associated with Syk activation (Y525/Y526) in all patients, and a VTE event in two patients. Plasma levels of DNA-histone complexes increased steadily after surgery and remained elevated throughout the study period. Additionally, we increasingly sighted both homotypic and heterotypic platelet microaggregates after surgery in CRC/MBD patients, but not in healthy control participants' plasma. Our data elucidates the cell biology of a prothrombo-inflammatory state caused by disease and vascular injury, and recalcitrant to thromboprophylaxis. New mechanistic insights into hypercoagulability in CRC/MBD patients may identify novel drug targets for effective thromboprophylaxis type and duration after orthopaedic surgery.

High SNAIL Expression Reflects Of Recurrence After Resection Colorectal Cancer Liver Metastasis

Introduction: Metastasectomy is one of the effective treatment methods for liver metastases developing from primary colorectal cancer (CRC). However, recurrence after metastasectomy is the biggest problem in these cancers. &#x0D; The present study aimed to examine the role of Epithelial-Mesenchymal Transition (EMT) in the development of recurrence after metastasectomy in liver metastases from primary CRCs.&#x0D; Materials and Methods: In the study, 85 patients were evaluated. RNA was isolated from archive tumors and normal tissues of the patients. Expression profiles of 7 different EMT markers were examined using qRT-PCR.&#x0D; Results: Metastasis to the liver developed in 24.7% (n=21) of 85 CRC. Recurrence was observed in 42.3% (n=9) of liver metastases after metastasectomy. Statistically significant increases were detected in the expression of EMT markers TWIST and SNAIL in the development of mCC in primary CRC (p

Analysis of Circulating Immune Subsets in Primary Colorectal Cancer.

The development and progression of colorectal cancer (CRC) are known to be affected by the interplay between tumor and immune cells. However, the impact of CRC cells on the systemic immunity has yet to be elucidated. We aimed to comprehensively evaluate the circulating immune subsets and transcriptional profiles of CRC patients. In contrast to healthy controls (HCs), CRC patients had a lower percentage of B and T lymphocytes, T helper (Th) cells, non-classical monocytes, dendritic cells, and a higher proportion of polymorphonuclear myeloid-derived suppressor cells, as well as a reduced expression of CD69 on NK cells. Therefore, CRC patients exhibit a more evident systemic immune suppression than HCs. A diagnostic model integrating seven immune subsets was constructed to distinguish CRC patients from HCs with an AUC of 1.000. Moreover, NR3C2, CAMK4, and TRAT1 were identified as candidate genes regulating the number of Th cells in CRC patients. The altered composition of circulating immune cells in CRC could complement the regional immune status of the tumor microenvironment and contribute to the discovery of immune-related biomarkers for the diagnosis of CRC.

Concurrent major hepatic resection with primary colorectal cancer increases risk of organ space infections.

Patients with colorectal cancer frequently present with liver metastases requiring either concurrent colon and liver resection or staged resection for curative therapy. The goal of this study is to determine if synchronous resection increases risk of perioperative adverse outcomes such as surgical site infections (SSIs). We conducted a cross-sectional retrospective analysis of the targeted hepatectomy NSQIP database from 2015 to 2019. The primary outcome was surgical site infections stratified into superficial, deep, organ space, and wound dehiscence. We performed univariate followed by a multivariate logistic regression to determine if there were higher odds of SSIs in patients undergoing hepatic resection concurrently with primary colorectal resection. Additionally, we performed stratified analyses by size of hepatic resections (partial, total left, total right, and trisegmentectomy). Of the 7,445 patients included in the study, 431(5.8%) underwent synchronous resection and 7,014 metachronous resection. On average, synchronous resections prolonged surgery by 62min. There was no difference in superficial and deep SSIs between the groups; however, there was a significant difference in organ space SSIs. Patients undergoing synchronous resection had 1.51 times the odds of developing an organ space SSI (OR 1.51, 95%CI 1.10, 2.17, p = 0.04) compared to patients with metachronous resection on multivariate analysis. Patients undergoing a total right hepatectomy concurrently with a colorectal resection had 2.30 times the odds of developing an organ space SSI (OR 2.30, 95%CI 1.20, 6.86, p = 0.010). Prior studies demonstrated that synchronous resections are safe in properly selected patients with no difference in long-term outcomes. Few studies have explored immediate perioperative outcomes between the two approaches. After controlling for confounders, we demonstrate that synchronous resection with major hepatic surgery increases the risk of organ space SSIs. Future studies should elucidate the precise source of organ space SSIs in order to decrease the risk of this adverse outcome.

CD318 is a target of chimeric antigen receptor T cells for the treatment of colorectal cancer.

Colorectal cancer (CRC) currently has a poor prognosis with a 6.9-year median survival time; to relieve this malignant cancer, we proposed to establish CRC xenografts that can be used to evaluate the cytotoxicity of adoptive chimeric antigen receptor (CAR)-T cells and accelerate the clinical translation of CAR-T cells for use against CRC. We first verified that CD318 had a higher expression level in primary human CRC tissues than in normal tissues based on hundreds of clinical samples. Then, we redirected CAR-T cells containing anti-CD318 single-chain variable fragment (anti-CD318 scFv), CD3ζ, CD28, and Toll-like receptor 2 (TLR2) domains. Next, we evaluated the function of these CAR-T cells in vitro in terms of surface phenotype changes, cytotoxicity and cytokine secretion when they encountered CD318+ CRC cells. Finally, we established two different xenograft mouse models to assess in vivo antitumor activity. The results showed that CAR318 T cells were significantly activated and exhibited strong cytotoxicity and cytokine-secreting abilities against CRC cells in vitro. Furthermore, CAR318 T cells induced CRC regression in different xenograft mouse models and suppressed tumors compared with CAR19 T cells. In summary, our work demonstrates that CAR318 T cells possess strong antitumor capabilities and represent a promising therapeutic approach for CRC.