Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival

Mlecnik, Bernhard; Eynde, Marc Van den; Bindea, Gabriela; Church, S.; Vasaturo, Angela; Fredriksen, Tessa; Lafontaine, Lucie; Haicheur, Nacilla; Marliot, Florence; Debetancourt, Daphné; Pairet, Géraldine; Jouret‐Mourin, Anne; Gigot, Jean‐François; Hubert, Catherine; Danse, Étienne; Dragean, Cristina; Carrasco, Javier; Humblet, Yves; Valge-Archer, Viia; Berger, Anne; Pagès, Franck; Machiels, Jean‐Pascal; Galon, Jérôme

doi:10.1093/jnci/djx123

Cited by 209 publications

(220 citation statements)

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“…After revision, 16 of these 24 papers were excluded for following reasons: eight studies did not provide HRs or CIs, seven studies were reviews, and one study was case report. Therefore, eight studies fulfilled our eligibility criteria for the analysis . Among them, one paper reported the results of two different population respectively, so it was treated as two studies for analysis.…”

Section: Resultsmentioning

confidence: 99%

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The prognostic value of immunoscore in patients with colorectal cancer: A systematic review and meta‐analysis

et al. 2018

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The tumor immune infiltrate, as recently evaluated with the immunoscore methodology, has been reported to be related to colorectal cancer (CRC) progression. Nevertheless, results varied from different studies. A meta‐analysis was conducted to solve this problem. We collected data from included studies to evaluate the prognostic role of immunoscore in CRC patients on overall survival (OS) and disease‐free survival (DFS). MEDLINE, EMBASE, and Cochrane libraries were searched through 30 June 2018. Hazard ratio (HR) with 95% confidence intervals (95% CI) was pooled using a random‐effects model for OS and a fixed‐effects model for DFS. Finally, eight studies (involving 4689 CRC cases) were identified as eligible publications. The results of the meta‐analysis showed that low immunoscore was significantly correlated with poor OS (HR = 1.74, 95% CI: 1.43‐2.13) and DFS (HR = 1.82, 95% CI: 1.64‐2.03). The findings from most subgroup analyses were consistent with those from the overall analysis. The immunoscore could be a useful prognostic marker in patients with CRC. It is necessary to evaluate immunological markers in international multicenter studies.

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Section: Resultsmentioning

confidence: 99%

“…Therefore, eight studies fulfilled our eligibility criteria for the analysis. 11,[21][22][23][24][25][26][27] Among them, one paper 24 reported the results of two different population respectively, so it was treated as two studies for analysis. Table 1 presented the characteristics of the eight included studies.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of immunoscore in patients with colorectal cancer: A systematic review and meta‐analysis

et al. 2018

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“…Intricate crosstalk between malignant cells and their neighboring cells such as tumor‐associated immune cells and fibroblasts in the tumor microenvironment critically dictates the initiation, progression and therapeutic response in human cancer . Recent exciting breakthrough and tremendous success in cancer immunotherapy have spurred great interests in identification, enumeration and functional interrogation of various TII cell subsets and reactivation of anticancer immunity . To achieve optimal outcomes of immunotherapy against cancer, comprehensive knowledge regarding location, density and functional status of TIIs might be a prerequisite .…”

Section: Discussionmentioning

confidence: 99%

“…Integrating multiple immune features into a single model would substantially improve the prognostic value and power over that of single biomarker . Indeed, comprehensive and simultaneous characterization of TIIs including types, densities, locations and functional orientations in solid tumors has been proposed as a novel and robust approach to predict clinical outcome . For example, the consensus immunoscore integrates the densities of CD3 + and CD8 + T‐cell effectors within tumor and its surrounding microenvironment, which has been revealed to better define patients’ prognosis, identify patients with high risk of recurrence and stratify patients who may benefit from adjuvant therapies .…”

Section: Introductionmentioning

confidence: 99%

“…[16][17][18][19] Indeed, comprehensive and simultaneous characterization of TIIs including types, densities, locations and functional orientations in solid tumors has been proposed as a novel and robust approach to predict clinical outcome. 7,11,16,20 For example, the consensus immunoscore integrates the densities of CD3 + and CD8 + T-cell effectors within tumor and its surrounding microenvironment, which has been revealed to better define patients' prognosis, identify patients with high risk of recurrence and stratify patients who may benefit from adjuvant therapies. 18,19 Moreover, Jiang et al 17 have developed a new five-feature-based ImmunoScore (IS) from 27 immune features by immunohistochemistry in 251 gastric cancers and verified that this IS classifier can effectively predict recurrence and survival, and complement the prognostic value of TNM staging system.…”

Section: Introductionmentioning

confidence: 99%

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Development and validation of a seven‐immune‐feature‐based prognostic score for oral squamous cell carcinoma after curative resection

Zhou

Diao

et al. 2019

Intl Journal of Cancer

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Immune infiltrates have been increasingly recognized as robust prognostic factors for human cancer. Here, we developed and validated a seven‐immune‐feature‐based prognostic score (7IFBPS) for patients with oral squamous cell carcinoma (OSCC) after curative resection. Fourteen immune features regarding detailed locations and densities of seven types of tumor‐infiltrating immune cells (TIIs) were characterized in clinical samples from 269 eligible patients in three independent cohorts by immunohistochemistry coupled with digital quantitation. Optimal cutoff values for individual immune features were yielded using X‐tile software. The 7IFBPS was constructed by Kaplan–Meier and Cox regression model in training cohort and verified in testing, validation and combined cohorts. Concordance index (C‐index), receiver operating characteristics and calibration curves were employed to define the performance of 7IFBPS in prognostic prediction. High CD3 IM (invasive margin), CD3 CT (center of tumor), CD8 CT, CD45RO IM, CD45RO CT, FOXP3 IM and FOXP3 CT significantly associated with improved survival. The 7IFBPS score was calculated using the formula: 1.041 × CD3 IM + 1.24 × CD3 CT + 1.701 × CD8 CT + 1.127 × CD45RO IM + 1.348 × CD45RO CT + 1.089 × FOXP3 IM + 1.483 FOXP3 CT. High 7IFBPS significantly associated with improved survival in all cohorts and served as an independent prognostic predictor. The C‐index of 7IFBPS for predicting survival was 0.668 (95% CI, 0.609–0.726). Calibration curves for survival probability showed good agreement between prediction by 7IFBPS and actual observation. Collectively, our findings established the 7IFBPS as a novel powerful prognostic classifier for resectable OSCC. It holds potentials to be incorporated into current prognostic regime to better patient stratification.

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Prognostic assessment of resected colorectal liver metastases integrating pathological features, RAS mutation and Immunoscore

Baldin

Eynde

Mlecnik

et al. 2020

The Journal of Pathology CR

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Surgical resection of colorectal liver metastases combined with systemic treatment aims to maximize patient survival. However, recurrence rates are very high postsurgery. In order to assess patient prognosis after metastasis resection, we evaluated the main patho‐molecular and immune parameters of all surgical specimens. Two hundred twenty‐one patients who underwent, after different preoperative treatment, curative resection of 582 metastases were analyzed. Clinicopathological parameters, RAS tumor mutation, and the consensus Immunoscore (I) were assessed for all patients. Overall survival (OS) and time to relapse (TTR) were estimated using the Kaplan–Meier method and compared by log‐rank tests. Cox proportional hazard models were used for uni‐ and multivariate analysis. Immunoscore and clinicopathological parameters (number of metastases, surgical margin, histopathological growth pattern, and steatohepatitis) were associated with relapse in multivariate analysis. Overall, pathological score (PS) that combines relevant clinicopathological factors for relapse, and I, were prognostic for TTR (2‐year TTR rate PS 0–1: 49.8.% (95% CI: 42.2–58.8) versus PS 2–4: 20.9% (95% CI: 13.4–32.8), hazard ratio (HR) = 2.54 (95% CI: 1.82–3.53), p < 0.0000; and 2‐year TTR rate I 0: 25.7% (95% CI: 16.3–40.5) versus I 3–4: 60% (95% CI: 47.2–76.3), HR = 2.87 (95% CI: 1.73–4.75), p = 0.0000). Immunoscore was also prognostic for OS (HR [I 3–4 versus I 0] = 4.25, 95% CI: 1.95–9.23; p = 0.0001). Immunoscore (HR [I 3–4 versus I 0] = 0.27, 95% CI: 0.12–0.58; p = 0.0009) and RAS mutation (HR [mutated versus WT] = 1.66, 95% CI: 1.06–2.58; p = 0.0265) were significant for OS. In conclusion, PS including relevant clinicopathological parameters and Immunoscore permit stratification of stage IV colorectal cancer patient prognosis in terms of TTR and identify patients with higher risk of recurrence. Immunoscore remains the major prognostic factor for OS.

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Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival

Abstract: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis.

Cited by 209 publications

References 50 publications

The prognostic value of immunoscore in patients with colorectal cancer: A systematic review and meta‐analysis

The prognostic value of immunoscore in patients with colorectal cancer: A systematic review and meta‐analysis

Development and validation of a seven‐immune‐feature‐based prognostic score for oral squamous cell carcinoma after curative resection

Prognostic assessment of resected colorectal liver metastases integrating pathological features, RAS mutation and Immunoscore

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