Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival. (25th August 2017)

• Record Type: Journal Article
• Authors: Mlecnik, Bernhard; Van den Eynde, Marc; Bindea, Gabriela; Church, Sarah E.; Vasaturo, Angela; Fredriksen, Tessa; Lafontaine, Lucie; Haicheur, Nacilla; Marliot, Florence; Debetancourt, Daphné; Pairet, Géraldine; Jouret-Mourin, Anne; Gigot, Jean-Francois; Hubert, Catherine; Danse, Etienne; Dragean, Cristina; Carrasco, Javier; Humblet, Yves; Valge-Archer, Viia; Berger, Anne; Pagès, Franck; Machiels, Jean-Pascal; Galon, Jérôme
• Is Part Of: Journal of the National Cancer Institute. Volume 110:Number 1(2018)
• Publication Date: 2017-08-25
• Subjects: Cancer -- Periodicals; Cancer -- Research -- Periodicals; 616.994
• DOI: 10.1093/jnci/djx123
• Languages: English
• ISSNs: 0027-8874

Abstract

Abstract: Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3–4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0–1–2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3–4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0–1–2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3–4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0–1–2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3–4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0–1–2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis ( P < .001), while response to treatment was not. Conclusions: 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.