Article ; Online: Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.
Journal of the National Cancer Institute
2017 Volume 110, Issue 1
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 ... ...
| 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. |
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| MeSH term(s) | Aged ; Antigens, CD20/analysis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; B-Lymphocytes/chemistry ; CD3 Complex/analysis ; CD8-Positive T-Lymphocytes ; Chemotherapy, Adjuvant ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/therapy ; Disease-Free Survival ; Follow-Up Studies ; Forkhead Transcription Factors/analysis ; Hepatectomy ; Humans ; Leukocyte Common Antigens/analysis ; Liver Neoplasms/immunology ; Liver Neoplasms/secondary ; Liver Neoplasms/therapy ; Lung Neoplasms/immunology ; Lung Neoplasms/secondary ; Lung Neoplasms/therapy ; Lymphocyte Count ; Lymphocytes, Tumor-Infiltrating ; Metastasectomy ; Middle Aged ; Neoplasm Metastasis ; Pneumonectomy ; Preoperative Period ; Response Evaluation Criteria in Solid Tumors ; Survival Rate ; T-Lymphocytes/chemistry ; Tumor Microenvironment/immunology | |||||
| Chemical Substances | Antigens, CD20 ; CD3 Complex ; FOXP3 protein, human ; Forkhead Transcription Factors ; Leukocyte Common Antigens (EC 3.1.3.48) | |||||
| Language | English | |||||
| Publishing date | 2017-09-27 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2992-0 | |||||
| ISSN | 1460-2105 ; 0027-8874 ; 0198-0157 | |||||
| ISSN (online) | 1460-2105 | |||||
| ISSN | 0027-8874 ; 0198-0157 | |||||
| DOI | 10.1093/jnci/djx123 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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