Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a surprising lack of agreement

Bohan, Phillip M. Kemp; Chick, Robert C.; Hickerson, Annelies T.; Messersmith, Lynn; Williams, Grant M.; Cindass, Jessica L.; Lombardo, Jamie; Collins, Ryan; Brady, Robert; Hale, Diane F.; Peoples, George E.; Vreeland, Timothy J.; Clifton, Guy T.

doi:10.1007/s00262-020-02784-5

Cited by 15 publications

(13 citation statements)

References 24 publications

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“…16,20,22,31 Notably, the inherent ITH of TME and PD-L1 status were reported to underlie the contradictory results obtained regarding the predictive value of immune status in clinical trials. 4,5,21 The ITH of TME and the low accuracy of TME evaluation based on biopsy in gastrointestinal malignancies, including gastroesophageal adenocarcinoma 32,33 and colorectal cancer, 34 those from a previous study. 20 Our findings, taken together with the results of prior studies highlighting the utility of small biopsy specimens in lung 16,35 and breast 36 cancers, suggest that tumor-surface information might reasonably be used for predicting the immune status of the whole tumor in ESCC.…”

Section: Horizontal Heterogeneitymentioning

confidence: 83%

“…The ITH of TME and the low accuracy of TME evaluation based on biopsy in gastrointestinal malignancies, including gastroesophageal adenocarcinoma 32 , 33 and colorectal cancer, 34 have been reported. Conversely, little is known about the ITH of TME and the potential of biopsy specimens for representing the immune status of the entire tumor in patients with ESCC.…”

Section: Discussionmentioning

confidence: 99%

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Influences of intratumoral heterogeneity on assessment of tumor microenvironment in esophageal squamous cell carcinoma

et al. 2022

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The intratumoral heterogeneity (ITH) of the tumor microenvironment (TME) has yet to be addressed in esophageal squamous cell carcinoma (ESCC). Here, we studied the ITH of CD8 and PD‐L1 status in ESCC, and examined the potential of the tumor surface for representing the TME. In total, 67 surgically resected clinical Stage II ESCC specimens were analyzed. The CD8‐cell density, PD‐L1 tumor proportion score (TPS), and combined positive score (CPS) were calculated in three (superficial, middle, and deep) areas of each specimen. ITH was quantified by distance‐standardized coefficient variations of the three values. The CD8 and PD‐L1 status of each area was dichotomized and tumor‐surface capabilities for predicting the entire tumor status were estimated. Variables were compared according to the presence of neoadjuvant chemotherapy (NAC). The ITH, especially PD‐L1 heterogeneity, differed markedly among specimens. The concordance rates of CD8 and PD‐L1 (CPS and TPS) status among the three different areas were 71.6%, 74.6%, and 73.1%, respectively. The sensitivity and the specificity of the tumor surface for predicting the CD8 status of the whole tumor were high, especially in the NAC− group (both 1.0). The tumor surface also showed high capabilities for representing the whole PD‐L1 status, while yielding moderate positive predictive values (0.70). The ITH degrees and predictive capabilities did not differ according to NAC. Taken together, the ITH of CD8 and PD‐L1 differed among ESCC specimens, while not being markedly affected by NAC. The use of a biopsy specimen from the tumor surface might be feasible for TME evaluation.

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Section: Horizontal Heterogeneitymentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Influences of intratumoral heterogeneity on assessment of tumor microenvironment in esophageal squamous cell carcinoma

et al. 2022

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“…However, some factors showed similar results at the tumor center and invasive front, whereas some factors did not [ 32 , 33 ]. Assessing TB inside the tumor, that is, ITB, yielded results similar to those obtained by evaluating this factor at the invasive front [ 34 ]; thus, ITB could be a prognostic biomarker in PBSs [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Intratumoral Budding in Pretreatment Biopsies, among Tumor Microenvironmental Components, Can Predict Prognosis and Neoadjuvant Therapy Response in Colorectal Adenocarcinoma

et al. 2022

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Background and Objectives: The prediction of the prognosis and effect of neoadjuvant therapy is vital for patients with advanced or unresectable colorectal carcinoma (CRC). Materials and Methods: We investigated several tumor microenvironment factors, such as intratumoral budding (ITB), desmoplastic reaction (DR), and Klintrup–Mäkinen (KM) inflammation grade, and the tumor–stroma ratio (TSR) in pretreatment biopsy samples (PBSs) collected from patients with advanced or unresectable CRC. A total of 85 patients with 74 rectal carcinomas and 11 colon cancers treated at our hospital were enrolled; 66 patients had curative surgery and 19 patients received palliative treatment. Results: High-grade ITB was associated with recurrence (p = 0.002), death (p = 0.034), and cancer-specific death (p = 0.034). Immature DR was associated with a higher grade of clinical tumor-node-metastasis stage (cTNM) (p = 0.045), cN category (p = 0.045), and cM category (p = 0.046). The KM grade and TSR were not related to any clinicopathological factors. High-grade ITB had a significant relationship with tumor regression in patients who received curative surgery (p = 0.049). Conclusions: High-grade ITB in PBSs is a potential unfavorable prognostic factor for patients with advanced CRC. Immature DR, TSR, and KM grade could not predict prognosis or therapy response in PBSs.

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“…It is important to note that only three studies have compared the tumor microenvironment of endoscopic biopsies and surgical specimens in CRC. [134][135][136] All three reports demonstrated a weak correlation between the biopsy tumor microenvironment with the tumor microenvironment present in the total resection specimen. As further studies are needed to focus on the clinical relevance of singular patient-derived explants (biopsies), it would help to map the tumor microenvironment by using multiple samples throughout the tumor, in addition to sampling before and after treatment to evaluate definitive effects of the therapy.…”

Section: Application Of Single-cell Multi-omics For Crc Cell Communic...mentioning

confidence: 99%

“…It is important to note that only three studies have compared the tumor microenvironment of endoscopic biopsies and surgical specimens in CRC 134–136 . All three reports demonstrated a weak correlation between the biopsy tumor microenvironment with the tumor microenvironment present in the total resection specimen.…”

Section: Application Of Single‐cell Multi‐omics For Crc Cell Communicmentioning

confidence: 99%

Understanding cell‐cell communication and signaling in the colorectal cancer microenvironment

AlMusawi

Ahmed

Nateri

2021

Clinical & Translational Med

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Carcinomas are complex heterocellular systems containing epithelial cancer cells, stromal fibroblasts, and multiple immune cell‐types. Cell‐cell communication between these tumor microenvironments (TME) and cells drives cancer progression and influences response to existing therapies. In order to provide better treatments for patients, we must understand how various cell‐types collaborate within the TME to drive cancer and consider the multiple signals present between and within different cancer types. To investigate how tissues function, we need a model to measure both how signals are transferred between cells and how that information is processed within cells. The interplay of collaboration between different cell‐types requires cell‐cell communication. This article aims to review the current in vitro and in vivo mono‐cellular and multi‐cellular cultures models of colorectal cancer (CRC), and to explore how they can be used for single‐cell multi‐omics approaches for isolating multiple types of molecules from a single‐cell required for cell‐cell communication to distinguish cancer cells from normal cells. Integrating the existing single‐cell signaling measurements and models, and through understanding the cell identity and how different cell types communicate, will help predict drug sensitivities in tumor cells and between‐ and within‐patients responses.

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Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a surprising lack of agreement

Cited by 15 publications

References 24 publications

Influences of intratumoral heterogeneity on assessment of tumor microenvironment in esophageal squamous cell carcinoma

Influences of intratumoral heterogeneity on assessment of tumor microenvironment in esophageal squamous cell carcinoma

Intratumoral Budding in Pretreatment Biopsies, among Tumor Microenvironmental Components, Can Predict Prognosis and Neoadjuvant Therapy Response in Colorectal Adenocarcinoma

Understanding cell‐cell communication and signaling in the colorectal cancer microenvironment

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