Whole-Slide Image Analysis Reveals Quantitative Landscape of Tumor–Immune Microenvironment in Colorectal Cancers

Yoo, Seung Seok; Kim, Jung Ho; Wen, Xianyu; Jeong, Seorin; Cho, Nam Yun; Gwon, Hwang Gwan; Kim, Kwangsoo; Lee, Hye Seung; Jeong, Seung Yong; Park, Kyu Joo; Han, Sae Won; Bae, Jeong Mo; Kang, Gyeong Hoon

doi:10.1158/1078-0432.ccr-19-1159

Cited by 46 publications

(45 citation statements)

References 49 publications

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“… 72 We anticipate that interest in γδ T cell subset analysis within tumors in situ will be invigorated with innovative technologies such as fully automated high-content imaging and quantitative whole-slide imaging analysis. 73 , 74 …”

Section: Tumor-infiltrating γδ T Cells: Friends or Foes?mentioning

confidence: 99%

Cancer immunotherapy with γδ T cells: many paths ahead of us

et al. 2020

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γδ T cells play uniquely important roles in stress surveillance and immunity for infections and carcinogenesis. Human γδ T cells recognize and kill transformed cells independently of human leukocyte antigen (HLA) restriction, which is an essential feature of conventional αβ T cells. Vγ9Vδ2 γδ T cells, which prevail in the peripheral blood of healthy adults, are activated by microbial or endogenous tumor-derived pyrophosphates by a mechanism dependent on butyrophilin molecules. γδ T cells expressing other T cell receptor variable genes, notably Vδ1, are more abundant in mucosal tissue. In addition to the T cell receptor, γδ T cells usually express activating natural killer (NK) receptors, such as NKp30, NKp44, or NKG2D which binds to stress-inducible surface molecules that are absent on healthy cells but are frequently expressed on malignant cells. Therefore, γδ T cells are endowed with at least two independent recognition systems to sense tumor cells and to initiate anticancer effector mechanisms, including cytokine production and cytotoxicity. In view of their HLA-independent potent antitumor activity, there has been increasing interest in translating the unique potential of γδ T cells into innovative cellular cancer immunotherapies. Here, we discuss recent developments to enhance the efficacy of γδ T cell-based immunotherapy. This includes strategies for in vivo activation and tumor-targeting of γδ T cells, the optimization of in vitro expansion protocols, and the development of gene-modified γδ T cells. It is equally important to consider potential synergisms with other therapeutic strategies, notably checkpoint inhibitors, chemotherapy, or the (local) activation of innate immunity.

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Section: Tumor-infiltrating γδ T Cells: Friends or Foes?mentioning

confidence: 99%

Cancer immunotherapy with γδ T cells: many paths ahead of us

et al. 2020

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“…We recently analyzed CD3 + TILs, CD8 + TILs, and the tumorstroma ratio (TSR) in 886 stage III or high-risk stage II CRCs using whole-slide imaging [22]. Clustering analysis using 197 parameters extracted from image analysis classified CRCs into five clusters.…”

Section: Quantitative Evaluation Of Time Using Digital Pathologymentioning

confidence: 99%

Immune landscape and biomarkers for immuno-oncology in colorectal cancers

Bae

Yoo

Kim

et al. 2020

J Pathol Transl Med

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Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the third leading cause of cancer-related death in Korea [1]. Because of rapid spread of colonoscopy screening, there was a general decrease in CRC until 2010. However, recent studies have reported that the decline in CRC incidence has reversed during the last few years, especially in middle-aged persons, and the occurrence of early-onset CRC has rapidly increased [2]. Most patients with CRC are diagnosed at an operable stage; however, approximately 20% of patients with stage III or high-risk stage II CRC relapse within 5 years after curative resection [3]. Moreover, the 5-year relative survival rate for metastatic CRC is 14% [2]. To improve clinical outcomes for patients with CRC, a more effective treatment modality is required to fulfill those unmet needs. Cancer is fundamentally a genetic disease since the accumulation of mutations, fusions, and copy number alterations drives tumorigenesis. However, recent research on the tumor immune microenvironment (TIME) has revealed the importance of interactions between tumor cells and surrounding immune cells in tumorigenesis [4]. Immune checkpoint inhibitor (ICI) treatment , such as anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies and anti-programmed death-1 (PD-1) antibodies, has shown marked clinical benefits in many types of cancer [5,6]. CRC also holds promise for cancer immunotherapy use, and the U.S. Food and Drug Administration (U.S. FDA) approved immunotherapeutic agents for microsatellite instability-high (MSI-H) CRC in 2017 (Fig. 1) [7,8]. In this review, we describe the landscape of the immune microenvironment in CRC and summarize the clinical usefulness of several suggested biomarkers in CRC immunotherapy. IMMUNE LANDSCAPE OF COLORECTAL CANCERS Historical use of microscopic evaluation of immune environment in CRCs To our knowledge, Spratt and Spjut [9] published the first study on integrative histologic evaluation of CRCs in 1967. In that study, the authors evaluated histologic grade, mucinous elements, depth of invasion, characteristics of tumor border, lym

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“… 16 , 28 , 29 Several semi-automated methods using IHC images to quantify TILs spatial distribution, such as Immunoscore, were proposed as independent prognostic factors for CRC. 7 , 8 , 30 Multiplexed immunofluorescence method was also used for automated image analysis, and multi-immune cells spatial interactions combination has been shown increased prognostic value. 9 , 10 In this context, we aimed to investigate the prognostic value of the rapid, fully automated pipeline-identified histogram features of IHC images in a multicentre population.…”

Section: Discussionmentioning

confidence: 99%

“… 7 A machine learning-based pipeline for quantifying intraepithelial and stromal tumor-infiltrating lymphocytes (iTILs and sTILs) was also established, which could subgroup resected and chemotherapy-treated CRCs. 8 While manual evaluation is indispensable during the Immunoscore calculation or TILs quantification process. As the semi-automatic scoring method, the process is not easily scalable.…”

Section: Introductionmentioning

confidence: 99%

Hist-Immune signature: a prognostic factor in colorectal cancer using immunohistochemical slide image analysis

Zhao

Yong

et al. 2020

OncoImmunology

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Computerized image analysis for whole-slide images has been shown to improve efficiency, accuracy, and consistency in histopathology evaluations. We aimed to assess whether immunohistochemistry (IHC) image quantitative features can reflect the immune status and provide prognostic information for colorectal cancer patients. A fully automated pipeline was designed to extract histogram features from IHC digital images in a training set (N = 243). A Hist-Immune signature was generated with selected features using the LASSO Cox model. The results were validated using internal (N = 147) and external (N = 76) validation sets. The five-feature-based Hist-Immune signature was significantly associated with overall survival in training (HR 2.72, 95% CI 1.68–4.41, P < .001), internal (2.86, 1.28–6.39, 0.010), and external (2.30, 1.02–6.16, 0.044) validation sets. The full model constructed by integrating the Hist-Immune signature and clinicopathological factors had good discrimination ability (C-index 0.727, 95% CI 0.678–0.776), confirmed using internal (0.703, 0.621–0.784) and external (0.756, 0.653–0.859) validation sets. Our findings indicate that the Hist-Immune signature constructed based on the quantitative features could reflect the immune status of patients with colorectal cancer, which might advocate change in risk stratification and consequent precision medicine.

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Whole-Slide Image Analysis Reveals Quantitative Landscape of Tumor–Immune Microenvironment in Colorectal Cancers

Cited by 46 publications

References 49 publications

Cancer immunotherapy with γδ T cells: many paths ahead of us

Cancer immunotherapy with γδ T cells: many paths ahead of us

Immune landscape and biomarkers for immuno-oncology in colorectal cancers

Hist-Immune signature: a prognostic factor in colorectal cancer using immunohistochemical slide image analysis

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