The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial

Flaherty, Devin C.; Jalas, John R.; Sim, Myung Shin; Stojadinovic, Alexander; Protić, Mladjan; Lee, Delphine J.; Bilchik, Anton J.

doi:10.1245/s10434-018-6405-x

Cited by 5 publications

(2 citation statements)

References 36 publications

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“…A comprehensive study of TIL/Tc infiltration abundance and geography, neoantigen specificity, clonal expansion and phenotypic subsets in the tumour niche is paramount to advancing our understanding of the mechanisms that drive tumour immune escape mechanisms. Additionally, due to the lack of detailed information about patient body mass index and systemic treatment in the cohorts we investigated, it was impossible to investigate any relationship between obesity and tumour infiltration [ 64 ] or determine the impact of different therapies on survival [ 38 ]. Therefore, we endorse validation in prospective series, particularly in the ICIs scenario, also using targeted TCR sequencing tools that, by increasing the detection power for TCR sequences [ 17 ], can facilitate the standardisation of optimal cut-offs and the qualification of TCR -based biomarkers.…”

Section: Discussionmentioning

confidence: 99%

T-Cell Infiltration and Clonality May Identify Distinct Survival Groups in Colorectal Cancer: Development and Validation of a Prognostic Model Based on The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC)

Campana

Mansoor

Hill

et al. 2022

Cancers

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Predicting the survival outcomes of patients with colorectal cancer (CRC) remains challenging. We investigated the prognostic significance of the transcriptome and tumour-infiltrating lymphocyte T-cell receptor (TIL/Tc-TCR) repertoire and analysed TIL/Tc-TCR sequences of The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) CRC cohorts. Using a multivariate Cox regression, we tested whether TIL/Tc-TCR repertoire, patient and tumour characteristics (stage, sidedness, total non-synonymous mutations, microsatellite instability (MSI) and transcriptional signatures) correlated with patient overall survival (OS) and designed a prognostic nomogram. A multivariate analysis (C-index = 0.75) showed that only patient age, disease stage, TIL/Tc degree of infiltration and clonality were independent prognostic factors for OS. The cut-offs for patients’ allocation to TIL/Tc abundance subgroups were determined using a strategy of maximally selected rank statistics with the OptimalCutpoints R package. These were “high”, “low” and “very high” (90 th percentile) TIL/Tc infiltration-stratified OS (median not reached, 67 and 44.3 months; p < 0.001); the results were validated in the CPTAC cohort. TIL/Tc clonality was prognostic (median OS in “high” vs. “low” clonality not reached and 67.3 months; p = 0.041) and independent of TIL/Tc infiltration. Whilst tumour sidedness was not prognostic, the “very highly” infiltrated tumours were prevalent among right-sided CRCs (p = 0.039) and showed distinct immunological features, with lower Th1 signature (p = 0.004), higher PD-L1 expression (p < 0.001) and likely enrichment in highly suppressory IL1R1+ Tregs (FoxP3 and IL1R1 overexpression, p < 0.001). TIL/Tc abundance and clonality are independent prognosticators in CRC and, combined with clinical variables, refine risk stratification. We identified a subset of CRCs with “very high” TIL/Tc infiltration, poor prognosis and distinct genetic and immunologic features, which may benefit from alternative therapeutic approaches. These results need validation in prospective patient cohorts.

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Section: Discussionmentioning

confidence: 99%

T-Cell Infiltration and Clonality May Identify Distinct Survival Groups in Colorectal Cancer: Development and Validation of a Prognostic Model Based on The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC)

Campana

Mansoor

Hill

et al. 2022

Cancers

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“…In recent years, a small subgroup of patients with CRC featuring mismatch repair deficiency (dMMR) were demonstrated to exhibit better outcomes than those with mismatch repair-proficient tumors (pMMR) in certain stage cases, such as stage II ( 60 , 61 ), and they also had a significantly good response when receiving immunotherapies in metastatic cases when compared to pMMR cases ( 62 ). Notably, a lower BMI was found to be more common in patients with dMMR than in those with pMMR ( 63 ); additionally, CEA levels were significantly higher in the pMMR subtype (but only in stage III patients) ( 64 ). These results suggested that for patients in certain stages, the CBR would be higher than for those in other stages.…”

Section: Discussionmentioning

confidence: 99%

Preoperative carcinoembryonic antigen to body mass index ratio contributes to prognosis prediction in colorectal cancer

et al. 2022

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Both carcinoembryonic antigen (CEA) level and body mass index (BMI) are traditional prognostic markers in colorectal cancer (CRC); however, to the best of our knowledge, the value of the CEA to BMI ratio (CBR) has never been addressed. In the present study, 191 patients with CRC treated using radical resection were retrospectively included, and the significance of the CBR in predicting disease-free survival (DFS) or overall survival (OS) rates was calculated. The prognostic efficacy of the CBR in predicting OS was compared with individual CEA and BMI values. The survival differences of the subgroups were calculated by Kaplan-Meier analysis, and corresponding risk factors were then estimated by a Cox proportional hazards model. As a result, 29.84% (57/191) of the patients were assigned to the high CBR group (cut-off, ≥0.28); the CBR had a sensitivity of 56.50 and 68.90%, and a specificity of 80.60 and 80.10% for DFS and OS, respectively. Patients with a high CBR more commonly underwent laparotomy and exhibited advanced T stages, the presence of tumor deposits and advanced Tumor-Node-Metastasis stages (stage II or III). The CBR was more efficient than the CEA or BMI alone in predicting OS. In addition, patients with a high CBR presented with a significantly worse outcome than patients with a low CBR. Finally, the CBR was an independent risk factor for both DFS and OS. In conclusion, the CBR was a more robust prognostic factor in CRC, and patients with a relatively high CBR exhibited poorer survival.

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Probiotic strain Lactobacillus plantarum YYC-3 prevents colon cancer in mice by regulating the tumour microenvironment

Yue

Yang

et al. 2020

Biomedicine & Pharmacotherapy

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The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial

Abstract: Tumor mismatch repair status and obesity are correlated in patients with colon cancer. Increased intratumoral T cells in nonobese patients suggests an unexplored link between tumor mismatch repair and immunoprofile.

Cited by 5 publications

References 36 publications

T-Cell Infiltration and Clonality May Identify Distinct Survival Groups in Colorectal Cancer: Development and Validation of a Prognostic Model Based on The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC)

T-Cell Infiltration and Clonality May Identify Distinct Survival Groups in Colorectal Cancer: Development and Validation of a Prognostic Model Based on The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC)

Preoperative carcinoembryonic antigen to body mass index ratio contributes to prognosis prediction in colorectal cancer

Probiotic strain Lactobacillus plantarum YYC-3 prevents colon cancer in mice by regulating the tumour microenvironment

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