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In Situ Cytotoxic And Memory T Cells Predict Outcome In Patients With Early-stage Colorectal Cancer.

F. Pagès, A. Kirilovsky, B. Mlecnik, M. Asslaber, M. Tosolini, G. Bindea, C. Lagorce, P. Wind, F. Marliot, P. Bruneval, K. Zatloukal, Z. Trajanoski, A. Berger, W. Fridman, J. Galon
Published 2009 · Medicine

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PURPOSE Many patients who present with early-stage colorectal cancer (International Union Against Cancer TNM stages I and II) are nevertheless at high risk of relapse. We hypothesized that intratumoral immune reaction could influence their prognosis. PATIENTS AND METHODS The intratumoral immune reaction was investigated in 29 tumors by large-scale real-time polymerase chain reaction. Cytotoxic (CD8) and memory (CD45RO) T cells were quantified by immunohistochemical analyses of tissue microarrays from the center (CT) and the invasive margin (IM) of the 602 tumors from two independent cohorts. The results were correlated with tumor recurrence and patient survival. RESULTS Patients with a strong infiltration of CD45RO(+) cells in the tumor exhibited an increased expression of T-helper 1 and cytotoxicity-related genes. Densities of CD45RO(+) and CD8(+) cells in tumor regions (CT/IM) classified the patients into four distinct prognostic groups based on the presence of high density of each marker in each tumor region. The four groups were associated with dramatic differences in disease-free, disease-specific, and overall survival (all P < .0001). Five years after diagnosis, only 4.8% (95% CI, 0.6% to 8.8%) of patients with high densities of CD8(+) plus CD45RO(+) cells had tumor recurrence, and 86.2% (CI, 79.4% to 93.6%) survived. In contrast, the tumor recurred in 75% (95% CI, 17% to 92.5%) of patients with low densities of these cells, and only 27.5% (95% CI, 10.5% to 72%) survived (all P < .0001). Multivariate analyses showed that the immune criteria had independent effects on the rates of complete remission and survival. CONCLUSION The combined analysis of CD8(+) plus CD45RO(+) cells in specific tumor regions could provide a useful criterion for the prediction of tumor recurrence and survival in patients with early-stage colorectal cancer.
This paper references
tection and clinical significance of occult tumour cells in colorectal cancer
G Tsavellas (2004)
10.3322/canjclin.55.2.74
Global Cancer Statistics, 2002
D. Parkin (2005)
10.3322/canjclin.56.2.106
Cancer Statistics, 2006
A. Jemal (2006)
10.1096/fj.01-0245com
Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells
J. Galon (2002)
10.1148/RADIOLOGY.207.1.66
TNM Classification of Malignant Tumors. 5th ed
R. Szucs (1998)
10.3322/caac.20107
Global cancer statistics
A. Jemal (2011)
10.1002/1097-0215(20001215)88:6<956::AID-IJC19>3.0.CO;2-3
T cell responses in colorectal cancer patients: Evidence for class II HLA‐restricted recognition of shared tumor‐associated antigens
A. J. Bremers (2000)
10.1136/jcp.39.6.585
Lymphocytic infiltration and survival in rectal cancer.
J. Jass (1986)
10.1158/0008-5472.CAN-06-4806
The adaptive immunologic microenvironment in colorectal cancer: a novel perspective.
J. Galon (2007)
10.1097/01.cco.0000198973.51615.fa
Tumor cell detection in peripheral blood and bone marrow
O. Zach (2006)
10.1200/JCO.2006.08.2644
ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer.
G. Locker (2006)
10.1038/nature06309
Adaptive immunity maintains occult cancer in an equilibrium state
Catherine M. Koebel (2007)
10.1002/(SICI)1096-9896(199707)182:3<318::AID-PATH862>3.0.CO;2-6
Prognostic value of tumour‐infiltrating lymphocytes (TILs) in colorectal cancer
K. Ropponen (1997)
10.1146/ANNUREV.IMMUNOL.22.012703.104702
Central memory and effector memory T cell subsets: function, generation, and maintenance.
F. Sallusto (2004)
10.1056/NEJMOA051424
Effector memory T cells, early metastasis, and survival in colorectal cancer.
F. Pagès (2005)
10.1002/(SICI)1097-0258(19961030)15:20<2203::AID-SIM357>3.0.CO;2-G
A simulation study of cross-validation for selecting an optimal cutpoint in univariate survival analysis.
D. Faraggi (1996)
10.1158/1078-0432.CCR-07-1380
Node-Negative Colorectal Cancer at High Risk of Distant Metastasis Identified by Combined Analysis of Lymph Node Status, Vascular Invasion, and Raf-1 Kinase Inhibitor Protein Expression
I. Zlobec (2008)
10.1200/JCO.2004.05.063
American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer.
A. Benson (2004)
10.1002/SIM.1611
Confidence intervals for the effect of a prognostic factor after selection of an 'optimal' cutpoint.
N. Hollaender (2004)
10.1093/JNCI/86.11.829
Dangers of using "optimal" cutpoints in the evaluation of prognostic factors.
D. Altman (1994)
10.1093/bioinformatics/18.1.207
Genesis: cluster analysis of microarray data
A. Sturn (2002)
10.1016/S0002-9440(10)61695-1
Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis.
M. Guidoboni (2001)
10.1038/sj.bjc.6600569
Role of biological markers in the clinical outcome of colon cancer
O. Nanni (2002)
10.1046/J.0007-1323.2001.01863.X
Detection and clinical significance of occult tumour cells in colorectal cancer
G. Tsavellas (2001)
Confidence intervals for the effect of a prognostic factor after selection of an “optimal
N Holländer (2004)
CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer.
Y. Naito (1998)
10.1007/978-3-642-82982-6
TNM Classification of Malignant Tumours
L. Sobin (1987)
10.1126/science.1129139
Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome
J. Galon (2006)



This paper is referenced by
10.3390/jpm9010003
Colorectal Cancer Biomarkers in the Era of Personalized Medicine
J. Patel (2019)
10.1093/JNCI/DJZ093
Immunotherapy for Colorectal Cancer: A Review of Current and Novel Therapeutic Approaches.
A. J. Franke (2019)
10.3389/fimmu.2018.01301
Genetically Induced Tumors in the Oncopig Model Invoke an Antitumor Immune Response Dominated by Cytotoxic CD8β+ T Cells and Differentiated γδ T Cells Alongside a Regulatory Response Mediated by FOXP3+ T Cells and Immunoregulatory Molecules
Nana H Overgaard (2018)
10.1186/s13000-017-0653-0
Computer-assisted stereology and automated image analysis for quantification of tumor infiltrating lymphocytes in colon cancer
A. C. Eriksen (2017)
10.3390/cancers11050633
Macrophages in Colorectal Cancer Liver Metastases
Nina Cortese (2019)
10.1007/s00281-011-0264-x
The prognostic impact of anti-cancer immune response: a novel classification of cancer patients
G. Bindea (2011)
Microenvironment and Immunology Modulation of Microenvironment Acidity Reverses Anergy in Human and Murine Tumor-In fi ltrating T Lymphocytes
Arianna Calcinotto (2012)
10.21037/atm.2016.07.07
Towards tumor immunodiagnostics.
H. Kourea (2016)
10.1007/s00262-016-1908-4
Heterogeneity of CD8+ tumor-infiltrating lymphocytes in non-small-cell lung cancer: impact on patient prognostic assessments and comparison of quantification by different sampling strategies
Joseph M. Obeid (2016)
10.1186/s12967-016-1070-y
Future perspectives in melanoma research
P. Ascierto (2013)
10.3390/jpm4010052
The Use of Registries to Improve Cancer Treatment: A National Database for Patients Treated with Interleukin-2 (IL-2)
H. Kaufman (2014)
10.1126/scitranslmed.aad6352
The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis
B. Mlecnik (2016)
10.18632/oncotarget.7282
Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer
Dong-qiang Zeng (2016)
10.1371/journal.pone.0159373
The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions
Antonella Maglietta (2016)
10.1038/s41586-019-1330-0
Immune evasion before tumour invasion in early lung squamous carcinogenesis
C. Mascaux (2019)
10.1186/1479-5876-11-145
Molecular signatures mostly associated with NK cells are predictive of relapse free survival in breast cancer patients
M. Ascierto (2013)
Enhanced effectiveness of conventional oncotherapy with plant immunomodulators: Overview of recent advances
T. Hajtó (2013)
10.3390/ijms21155255
Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review
Stanislav Filip (2020)
10.1007/s12307-012-0124-9
The Immune Microenvironment of Human Tumors: General Significance and Clinical Impact
W. Fridman (2012)
10.1038/bjc.2011.189
The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis
M. Gooden (2011)
10.1016/j.semcancer.2017.09.006
The Society for Immunotherapy of Cancer Biomarkers Task Force recommendations review.
L. Butterfield (2018)
10.1016/B978-0-12-416603-5.00017-1
Immunostimulators and Immunomodulators in Cancer Treatment
Brianna Oliver (2015)
10.1038/cgt.2013.5
New targets for the immunotherapy of colon cancer—does reactive disease hold the answer?
V. Boncheva (2013)
10.1200/JCO.2012.45.2052
Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor β2 (IL-12Rβ2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence.
K. Suzuki (2013)
10.1007/s00262-011-1133-0
Epitope-targeted cytotoxic T cells mediate lineage-specific antitumor efficacy induced by the cancer mucosa antigen GUCY2C
A. Snook (2011)
10.1186/1479-5876-11-54
The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment
P. Ascierto (2013)
10.14712/18059694.2019.129
Interactions Between Anti-Vegf Therapy and Antitumor Immunity as a Potential Therapeutic Strategy in Colorectal Cancer.
D. Buka (2019)
10.1038/s41598-019-48140-1
Clinical significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with stage III colon cancer who underwent surgery followed by FOLFOX chemotherapy
Y. Cha (2019)
10.3389/fimmu.2015.00582
Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens
M. Hebeisen (2015)
10.1186/s12885-018-4064-8
The effect of propofol and sevoflurane on cancer cell, natural killer cell, and cytotoxic T lymphocyte function in patients undergoing breast cancer surgery: an in vitro analysis
J. Lim (2018)
Genetic and clinical prognostic markers for colorectal cancer
M. A. Merok (2014)
10.1007/978-981-10-6020-5_17
New Approaches in CAR-T Cell Immunotherapy for Breast Cancer.
J. Wang (2017)
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