Comparison of Immune Response Assessment in Colon Cancer by Immunoscore (Automated Digital Pathology) and Pathologist Visual Scoring

Boquet, Isabelle; Kassambara, Alboukadel; Lui, Alfred; Tanner, Alicia; Latil, Marie; Lovera, Yoann; Arnoux, Fanny; Hermitte, Fabienne; Galon, Jérôme; Catteau, Aurélie

doi:10.3390/cancers14051170

Cited by 8 publications

(16 citation statements)

References 30 publications

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“…LN staging in contemporary clinical practice is binary; nodes are either infiltrated with cancer or not. This study, along with previous work on the prognostic value of looking at immune compartments in pathological samples, suggests that LN infiltration represents a spectrum of disease (Boquet et al., 2022; Galon et al., 2012; Pagès et al., 2018).…”

Section: Discussionsupporting

confidence: 69%

Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis

Brassard

Bartolomucci

et al. 2023

J of Extracellular Vesicle

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Lymph nodes (LNs) are frequently the first sites of metastasis. Currently, the only prognostic LN assessment is determining metastatic status. However, there is evidence suggesting that LN metastasis is facilitated by the formation of a pre‐metastatic niche induced by tumour derived extracellular vehicles (EVs). Therefore, it is important to detect and modify the LN environmental changes. Earlier work has demonstrated that neutrophil extracellular traps (NETs) can sequester and promote distant metastasis. Here, we first confirmed that LN NETs are associated with reduced patient survival. Next, we demonstrated that NETs deposition precedes LN metastasis and NETs inhibition diminishes LN metastases in animal models. Furthermore, we discovered that EVs are essential to the formation of LN NETs. Finally, we showed that lymphatic endothelial cells secrete CXCL8/2 in response to EVs inducing NETs formation and the promotion of LN metastasis. Our findings reveal the role of EV‐induced NETs in LN metastasis and provide potential immunotherapeutic vulnerabilities that may occur early in the metastatic cascade.

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Section: Discussionsupporting

confidence: 69%

Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis

Brassard

Bartolomucci

et al. 2023

J of Extracellular Vesicle

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“…LN staging in contemporary clinical practice is binary; nodes are either infiltrated with cancer or not. This study, along with previous work on the prognostic profundity of looking art immune compartment in pathological samples, suggests LN infiltration represents a spectrum of disease [78][79][80] .…”

Section: Discussionsupporting

confidence: 64%

Tumour Extracellular Vesicles Induce Neutrophil Extracellular Traps To Promote Lymph Node Metastasis

Brassard

Bartolomucci

et al. 2023

Preprint

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Lymph nodes (LNs) are frequently the first sites of metastasis. Currently, the only prognostic LN assessment is determining metastasis status. However, there is evidence suggesting that LN metastasis is facilitated by a pre-metastatic niche induced by tumour derived extracellular vehicles (EVs). Therefore, it is important to detect and modify the LN environmental changes. We have previously reported that neutrophil extracellular traps (NETs) can sequester and promote distant metastasis. Here, we first confirmed that LN NETs are associated with reduced patient survival. Next, we demonstrated that NETs deposition precedes LN metastasis and NETs inhibition abolishes LN metastases in animal mode. Furthermore, we discovered that EVs are essential to the formation of LN NETs. Lymphatic endothelial cells secrete CXCL8/2 in response to EVs inducing NETs formation and the promotion of LN metastasis. Our findings are the first to reveal the role of EV induced NETs in LN metastasis and provide potential immunotherapeutic vulnerabilities.

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“…Indeed, a weak concordance was previously reported between pathologist visual scoring of the CD3+ and CD8+ T-cell densities at the tumor site and Immunoscore for early-stage colon cancer and minimal agreement among pathologists was observed. 36 However, whether a digital assessment might better quantify TILs leading to a more suitable evaluation of their predictive value for ICIs efficacy in mCRC remains to be established. To this regard, a recent retrospective study showed that a machine learning-based analysis of H&E digital images of patients with metastatic NSCLC treated with single-agent ICIs found a higher response rates and longer PFS and OS in tumors with higher levels of TILs.…”

Section: Discussionmentioning

confidence: 99%

Dissecting tumor lymphocyte infiltration to predict benefit from immune-checkpoint inhibitors in metastatic colorectal cancer: lessons from the AtezoT RIBE study

Moretto

Rossini

Catteau³

et al. 2023

J Immunother Cancer

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BackgroundTumor immune cells influence the efficacy of immune-checkpoint inhibitors (ICIs) and many efforts aim at identifying features of tumor immune microenvironment able to predict benefit from ICIs in proficient mismatch repair (pMMR)/microsatellite stable (MSS) metastatic colorectal cancer (mCRC).MethodsWe characterized tumor immune cell infiltrate, by assessing tumor-infiltrating lymphocytes (TILs), Immunoscore, Immunoscore-IC, and programmed death ligand-1 (PD-L1) expression in tumor samples of patients with mCRC enrolled in the AtezoTRIBE study, a phase II randomized trial comparing FOLFOXIRI/bevacizumab/atezolizumab to FOLFOXIRI/bevacizumab, with the aim of evaluating the prognostic and predictive value of these features.ResultsOut of 218 patients enrolled, 181 (83%), 77 (35%), 157 (72%) and 162 (74%) specimens were successfully tested for TILs, Immunoscore, Immunoscore-IC and PD-L1 expression, respectively, and 69 (38%), 45 (58%), 50 (32%) and 21 (13%) tumors were classified as TILs-high, Immunoscore-high, Immunoscore-IC-high and PD-L1-high, respectively. A poor agreement was observed between TILs and Immunoscore or Immunoscore-IC (K of Cohen <0.20). In the pMMR population, longer progression-free survival (PFS) was reported for Immunoscore-high and Immunoscore-IC-high groups compared with Immunoscore-low (16.4 vs 12.2 months; HR: 0.55, 95% CI: 0.30 to 0.99; p=0.049) and Immunoscore-IC-low (14.8 vs 11.5 months; HR: 0.55, 95% CI: 0.35 to 0.85; p=0.007), respectively, with a significant interaction effect between treatment arms and Immunoscore-IC (p for interaction: 0.006) and a trend for Immunoscore (p for interaction: 0.13). No PFS difference was shown according to TILs and PD-L1 expression. Consistent results were reported in the overall population.ConclusionsThe digital evaluation of tumor immune cell infiltrate by means of Immunoscore-IC or Immunoscore identifies the subset of patients with pMMR mCRC achieving more benefit from the addition of the anti-PD-L1 to the upfront treatment. Immunoscore-IC stands as the most promising predictor of benefit from ICIs.

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Comparison of Immune Response Assessment in Colon Cancer by Immunoscore (Automated Digital Pathology) and Pathologist Visual Scoring

Cited by 8 publications

References 30 publications

Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis

Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis

Tumour Extracellular Vesicles Induce Neutrophil Extracellular Traps To Promote Lymph Node Metastasis

Dissecting tumor lymphocyte infiltration to predict benefit from immune-checkpoint inhibitors in metastatic colorectal cancer: lessons from the AtezoT RIBE study

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