Immunity, immunotherapy, and rectal cancer: A clinical and translational science review

Otegbeye, Ebunoluwa; Mitchem, Jonathan B.; Chaudhuri, Aadel A.; Kim, Hyun; Mutch, Matthew G.; Ciorba, Matthew A.

doi:10.1016/j.trsl.2020.12.002

Cited by 12 publications

(15 citation statements)

References 143 publications

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“…In contrast, low-risk patients exhibit higher sensitivity to gemcitabine. Rectal cancer displays high infiltration levels of tumor-infiltrating lymphocytes, particularly CD8 + T cells that are in relation to favorable survival outcomes ( Otegbeye et al, 2021 ). This suggests that cytotoxic antitumor immune responses participate in modulating tumor development.…”

Section: Discussionmentioning

confidence: 99%

Development of an Aging-Related Gene Signature for Predicting Prognosis, Immunotherapy, and Chemotherapy Benefits in Rectal Cancer

Wang

Liu

Zhu

et al. 2022

Front. Mol. Biosci.

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Objective: Aging is the major risk factor for human cancers, including rectal cancer. Targeting the aging process provides broad-spectrum protection against cancers. Here, we investigate the clinical implications of aging-related genes in rectal cancer.Methods: Dysregulated aging-related genes were screened in rectal cancer from TCGA project. A LASSO prognostic model was conducted, and the predictive performance was evaluated and externally verified in the GEO data set. Associations of the model with tumor-infiltrating immune cells, immune and stromal score, HLA and immune checkpoints, and response to chemotherapeutic agents were analyzed across rectal cancer. Biological processes underlying the model were investigated through GSVA and GSEA methods. Doxorubicin (DOX)-induced or replicative senescent stromal cells were constructed, and AGTR1 was silenced in HUVECs. After coculture with conditioned medium of HUVECs, rectal cancer cell growth and invasion were investigated.Results: An aging-related model was established, consisting of KL, BRCA1, CLU, and AGTR1, which can stratify high- and low-risk patients in terms of overall survival, disease-free survival, and progression-free interval. ROC and Cox regression analyses confirmed that the model was a robust and independent predictor. Furthermore, it was in relation to tumor immunity and stromal activation as well as predicted the responses to gemcitabine and sunitinib. AGTR1 knockdown ameliorated stromal cell senescence and suppressed senescent stromal cell-triggered rectal cancer progression.Conclusion: Our findings suggest that the aging-related gene signature was in relation to tumor immunity and stromal activation in rectal cancer, which might predict survival outcomes and immuno- and chemotherapy benefits.

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Section: Discussionmentioning

confidence: 99%

Development of an Aging-Related Gene Signature for Predicting Prognosis, Immunotherapy, and Chemotherapy Benefits in Rectal Cancer

Wang

Liu

Zhu

et al. 2022

Front. Mol. Biosci.

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“…CRC is a collection of several tumors, including rectum adenocarcinoma (READ), COAD, and other subtypes. In fact, prognostic properties and patterns differ from different subtypes of cancer, especially READ and COAD, which differ significantly in tumor progression, tumor microenvironment, and clinical treatment ( 21 – 26 ). Therefore, we concentrated on COAD, the subtypes of CRC alone, expecting to get more accurate understanding.…”

Section: Discussionmentioning

confidence: 99%

A Novel Pyroptosis-Related Gene Signature for Predicting the Prognosis and the Associated Immune Infiltration in Colon Adenocarcinoma

et al. 2022

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BackgroundPyroptosis has been demonstrated to be an inflammatory form of programmed cell death recently. However, the expression of pyroptosis-related genes (PRGs) in colon adenocarcinoma (COAD) and their correlations with prognosis remain unclear.MethodsData of COAD patients were obtained from The Cancer Genome Atlas (TCGA) database to screen differentially expressed genes (DEGs). Univariate Cox regression analysis and the LASSO Cox regression analysis were applied to construct a gene signature. All COAD patients in TCGA cohort were separated into low-risk subgroup or high-risk subgroup via the risk score. Kaplan–Meier survival analysis and receiver operator characteristic (ROC) curves were adopted to assess its prognostic efficiency. COAD data from the GSE17537 datasets was used for validation. A prognostic nomogram was established to predict individual survival. The correlation between PRGs and immune cell infiltration in COAD was verified based on TIMER database. CIBERSORT analysis was utilized on risk subgroup as defined by model. The protein and mRNA expression level of PRGs were verified by HPA database and qPCR.ResultsA total of 51 differentially expressed PRGs were identified in TCGA cohort. Through univariate Cox regression analysis and LASSO Cox regression analysis, a prognostic model containing 7 PRGs was constructed. Kaplan–Meier survival analysis indicated that patients in the low-risk subgroup exhibited better prognosis compared to those in the high-risk subgroup. Additionally, the area under the curve (AUC) of ROC is 0.60, 0.63, and 0.73 for 1-, 3-, and 5-year survival in TCGA cohort and 0.63, 0.65, and 0.64 in validation set. TIMER database showed a strong correlation between 7 PRGs and tumor microenvironment in COAD. Moreover, CIBERSORT showed significant differences in the infiltration of plasma cells, M0 macrophages, resting dendritic cells, and eosinophils between low-risk subgroup and high-risk subgroup. HPA database showed that protein expression level of SDHB, GZMA, BTK, EEF2K, and NR1H2 was higher in normal tissues. And the transcriptional level of CASP5, BTK, SDHB, GZMA, and RIPK3 was high in normal tissues.ConclusionsOur study identified a novel PRGs signature that could be used to predict the prognosis of COAD patients, which might provide a new therapeutic target for the treatment of COAD patients.

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“…The current standard treatment of rectal cancer consists of neoadjuvant chemoradiotherapy followed by surgery. Novel strategies included total neoadjuvant treatment, 51 watch and wait strategies, 52 and immunotherapy 53 . Three recent studies investigated the impact of MSI on neoadjuvant chemotherapy (NCT) treatment 41,54,55 and found conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Microsatellite instability in rectal cancer: what does it mean? A study of two randomized trials and a systematic review of the literature

et al. 2022

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Microsatellite instability in rectal cancer: what does it mean? A study of two randomized trials and a systematic review of the literature Aim: Currently, compelling evidence illustrates the significance of determining microsatellite instability (MSI) in colorectal cancer (CRC). The association of MSI with proximal CRC is well established, however, its implications in patients with rectal cancer remain undefined. We therefore aimed to determine the role of MSI with respect to incidence and outcome in patients with rectal cancer. Methods and Results: For this we examined patients from two prospective phase III trials: TME trial and PROCTOR-SCRIPT trial (n = 1250). In addition, we performed a literature review to evaluate the overall prevalence, the effect on survival and the response to neo-adjuvant treatment in patients with MSI rectal cancer compared with microsatellite stable (MSS) rectal cancer. Our TME and PROCTOR-SCRIPT cohort showed no differences in terms of overall survival (OS) (hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.69-1.47) and disease-free survival (DFS) (HR 1.00, 95% CI 0.68-1.45) in patients with MSI compared to MSS rectal cancer. The total number of MSI cases in all included studies (including our own) was 1220 (out of 16,526 rectal cancer patients), with an overall prevalence of 6.7% (standard error 1.19%). Both for OS as for DFS there was no impact of MSI status on prognosis (HR 1.00, respectively). The risk ratio (RR) for downstaging and pathological complete response showed also no impact of MSI status (RR 1.15, 95% CI 0.86-1.55 and RR 0.81, 95% CI 0.54-1.22, respectively). Conclusion: Rectal cancer patients with MSI form a distinct and rare subcategory, however, there is no prognostic effect of MSI in rectal cancer patients.

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Immunity, immunotherapy, and rectal cancer: A clinical and translational science review

Cited by 12 publications

References 143 publications

Development of an Aging-Related Gene Signature for Predicting Prognosis, Immunotherapy, and Chemotherapy Benefits in Rectal Cancer

Development of an Aging-Related Gene Signature for Predicting Prognosis, Immunotherapy, and Chemotherapy Benefits in Rectal Cancer

A Novel Pyroptosis-Related Gene Signature for Predicting the Prognosis and the Associated Immune Infiltration in Colon Adenocarcinoma

Microsatellite instability in rectal cancer: what does it mean? A study of two randomized trials and a systematic review of the literature

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