Histopathologic-Based Prognostic Factors of Colorectal Cancers Are Associated With the State of the Local Immune Reaction
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Purpose: The prognosis of patients with colorectal cancer has sometimes proved uncertain; thus, the prognostic significance of immune criteria was compared with that of the tumor extension criteria using the American Joint Committee on Cancer/International Union Against Cancer–TNM (AJCC/UICC-TNM) staging system. Patients and Methods: We studied the intratumoral immune infiltrates in the center of the tumor and in the invasive margin of 599 specimens of stage I to IV colorectal cancers from two independent cohorts. We analyzed these findings in relation to the degree of tumor extension and to the frequency of recurrence. Results: Growth of the primary tumor and metastatic spread were associated with decreased intratumoral immune T-cell densities. Sixty percent of patients with high densities of CD8 + cytotoxic T-lymphocyte infiltrate presented with stage Tis/T1 tumor, whereas no patients with low densities presented with such early-stage tumor. In patients who did not relapse, the density of CD8 infiltrates was inversely correlated with T stage. In contrast, in patients whose tumor recurred, the number of CD8 cells was low regardless of the T stage of the tumor. Univariate analysis showed that the immune score was significantly associated with differences in disease-free, disease-specific, and overall survival (hazard ratio [HR], 0.64, 0.60, and 0.70, respectively; P < .005). Time-dependent receiver operating characteristic curve analysis illustrated the predictive accuracy of the immune parameters (c-index = 65.3%, time-dependent c-index [Cτ] = 66.5%). A final stepwise model for Cox multivariate analysis supports the advantage of the immune score (HR, 0.64; P < .001; Cτ = 67.9%) compared with histopathologic features in predicting recurrence as well as survival. Conclusion: Assessment of CD8 + cytotoxic T lymphocytes in combined tumor regions provides an indicator of tumor recurrence beyond that predicted by AJCC/UICC-TNM staging.
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The spatial distribution of lymphocytes with respect to tumor, tumor boundary and tumor associated stroma are also important factors in cancer prognosis.
“The spatial distribution of lymphocytes with respect to tumor, tumor boundary and tumor associated stroma are also important factors in cancer prognosis [180].”
From AI in Medical Imaging Informatics: Current Challenges and Future Directions (2020) · cites this paper as [180]
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- Authors
- Mlecnik, B., Tosolini, M., Kirilovsky, A., Berger, A., Bindea, G., Meatchi, T., Bruneval, P., Trajanoski, Z., Fridman, W.-H., Pagès, F., & Galon, J.
- Affiliations
- Innsbruck Medical University (AT)
- From the Institut National de la Santé et de la Recherche Médicale, Integrative Cancer Immunology Team and Team 13 (INSERM U872); Université Paris Descartes; Cordeliers Research Center, Université Pierre et Marie Curie Paris 6; Hôpital Européen Georges Pompidou, Paris, France; and Biocenter, Section for Bioinformatics, Innsbruck Medical University, Innsbruck, Austria.
- Corresponding author
- Galon, Jérôme
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2011-02-20
- Volume
- 29
- Issue
- 6
- Pages
- 610-618
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2170137783
- Cited by
- 1,009
- References
- 4
- Citations by year
- 2026: 21 · 2025: 46 · 2024: 35 · 2023: 65 · 2022: 83 · 2021: 94 · 2020: 113 · 2019: 75 · 2018: 67 · 2017: 70 · 2016: 78 · 2015: 81 · 2014: 46 · 2013: 75 · 2012: 39
- FWCI
- 28.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- Association pour la Recherche sur le Cancer
- European Commission (202230)
- Institut National de la Santé et de la Recherche Médicale
- Institut National Du Cancer
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- colorectal cancer, prognostic factors, tumor-infiltrating lymphocytes, CD8+ cytotoxic T lymphocytes, tumor recurrence, metastasis, survival prediction, immune score
- MeSH terms
- Female, Humans, Immunologic Memory, Male, Middle Aged, Neoplasm Staging, Prognosis, ROC Curve, Colorectal Neoplasms, Proportional Hazards Models, Lymphocytes, Tumor-Infiltrating, CD8-Positive T-Lymphocytes, Disease-Free Survival, Tissue Array Analysis, Kaplan-Meier Estimate
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