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[PMID]: | 28922789 |
[Au] Autor: | Mlecnik B; Van den Eynde M; Bindea G; Church SE; Vasaturo A; Fredriksen T; Lafontaine L; Haicheur N; Marliot F; Debetancourt D; Pairet G; Jouret-Mourin A; Gigot JF; Hubert C; Danse E; Dragean C; Carrasco J; Humblet Y; Valge-Archer V; Berger A; Pagès F; Machiels JP; Galon J |
[Ad] Endereço: | Laboratory of Integrative Cancer Immunology, INSERM, UMRS1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMRS1138, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS1138, Centre de Recherche des Cordeliers, Paris, France; Inovarion, Paris, France; Department of Medic |
[Ti] Título: | Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival. |
[So] Source: | J Natl Cancer Inst;110(1), 2018 Jan 01. | [Is] ISSN: | 1460-2105 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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. |
[Mh] Termos MeSH primário: |
Linfócitos B Neoplasias Colorretais/imunologia Neoplasias Hepáticas/imunologia Neoplasias Pulmonares/imunologia Linfócitos do Interstício Tumoral Linfócitos T
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[Mh] Termos MeSH secundário: |
Idoso Antígenos CD20/análise Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Linfócitos B/química Complexo CD3/análise Linfócitos T CD8-Positivos Quimioterapia Adjuvante Neoplasias Colorretais/patologia Neoplasias Colorretais/terapia Intervalo Livre de Doença Seguimentos Fatores de Transcrição Forkhead/análise Hepatectomia Seres Humanos Antígenos Comuns de Leucócito/análise Neoplasias Hepáticas/secundário Neoplasias Hepáticas/terapia Neoplasias Pulmonares/secundário Neoplasias Pulmonares/terapia Contagem de Linfócitos Metastasectomia Meia-Idade Metástase Neoplásica Pneumonectomia Período Pré-Operatório Critérios de Avaliação de Resposta em Tumores Sólidos Taxa de Sobrevida Linfócitos T/química Microambiente Tumoral/imunologia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Antigens, CD20); 0 (CD3 Complex); 0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors); EC 3.1.3.48 (Leukocyte Common Antigens) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 180308 |
[Lr] Data última revisão:
| 180308 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170920 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1093/jnci/djx123 |
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