Analysis of the T Cell Receptor Variability of Tumor-Infiltrating Lymphocytes in Colorectal Carcinomas

Baier, P.; Wimmenauer, S.; Hirsch, Thomas; Specht, B U von; Kleist, S. von; Keller, H.; Farthmann, E. H.

doi:10.1159/000030008

Cited by 28 publications

(11 citation statements)

References 16 publications

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“…However, lymphocytes were also shown to participate in antitumoral responses (8). Consistent with findings in melanoma (9) and ovarian cancer (10,11), tumor-infiltrating T cells were associated with improved clinical outcome and survival in colorectal cancer patients (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 55%

Coordination of Intratumoral Immune Reaction and Human Colorectal Cancer Recurrence

Camus

Tosolini²,

Mlecnik³

et al. 2009

Cancer Research

262

222

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A role for the immune system in controlling the progression of solid tumors has been established in several mouse models. However, the effect of immune responses and tumor escape on patient prognosis in the context of human cancer is poorly understood. Here, we investigate the cellular and molecular parameters that could describe in situ immune responses in human colorectal cancer according to clinical parameters of metastatic lymph node or distant organ invasion (METAÀ or META+ patients). Primary tumor samples of colorectal carcinoma were analyzed by integrating large-scale phenotypic ( flow cytometry, 39 patients) and gene expression (real time reverse transcription-PCR, 103 patients) data sets related to immune and protumoral processes. In METAÀ colorectal cancer primary tumors with high densities of T cells, we observed significant positive correlations between markers of innate immune cells [tumor-associated macrophages, dendritic cells, natural killer (NK) cells, and NKT cells] and markers of early-activated T cells. Significant correlations were also observed between markers of cytotoxic and effector memory T-cell subpopulations. These correlation profiles were absent in tumors with low T-cell infiltrates and were altered in META+ tumors with high T-cell infiltrates. We show that the coexpression of genes mediating cytotoxicity (GNLY) and Th1 adaptive immune responses (IRF1) accurately predicted patient survival independently of the metastatic status. High intratumoral mRNA expression of the proangiogenic mediator vascular endothelial growth factor was associated with significantly reduced survival rates in patients expressing high mRNA levels of GNLY. Investigation of the colorectal cancer primary tumor microenvironment allowed us to uncover the association of favorable outcomes with efficient coordination of the intratumoral immune response.

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Section: Introductionmentioning

confidence: 55%

Coordination of Intratumoral Immune Reaction and Human Colorectal Cancer Recurrence

Camus

Tosolini²,

Mlecnik³

et al. 2009

Cancer Research

262

222

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“…Although it is well-established that the immune contexture may elicit both pro- and anti-tumorigenic responses, a growing body of evidence indicates that the presence of abundant tumor-infiltrating leukocytes, within established tumors, foretells favorable prognosis. This association has been rigorously documented for a number of malignancies, most notably cancers of the skin [38,39], ovary [40,41], colon [42-45] and breast [20-22], underscoring the broad protective effects of anti-cancer immunosurveillance [46-48]. …”

Section: Discussionmentioning

confidence: 99%

Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis

et al. 2013

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BackgroundGene expression signatures indicative of tumor proliferative capacity and tumor-immune cell interactions have emerged as principal biology-driven predictors of breast cancer outcomes. How these signatures relate to one another in biological and prognostic contexts remains to be clarified.ResultsTo investigate the relationship between proliferation and immune gene signatures, we analyzed an integrated dataset of 1,954 clinically annotated breast tumor expression profiles randomized into training and test sets to allow two-way discovery and validation of gene-survival associations. Hierarchical clustering revealed a large cluster of distant metastasis-free survival-associated genes with known immunological functions that further partitioned into three distinct immune metagenes likely reflecting B cells and/or plasma cells; T cells and natural killer cells; and monocytes and/or dendritic cells. A proliferation metagene allowed stratification of cases into proliferation tertiles. The prognostic strength of these metagenes was largely restricted to tumors within the highest proliferation tertile, though intrinsic subtype-specific differences were observed in the intermediate and low proliferation tertiles. In highly proliferative tumors, high tertile immune metagene expression equated with markedly reduced risk of metastasis whereas tumors with low tertile expression of any one of the three immune metagenes were associated with poor outcome despite higher expression of the other two metagenes.ConclusionsThese findings suggest that a productive interplay among multiple immune cell types at the tumor site promotes long-term anti-metastatic immunity in a proliferation-dependent manner. The emergence of a subset of effective immune responders among highly proliferative tumors has novel prognostic ramifications.

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“…Mouse experiments confirm a role of T cells in cancer immune surveillance 2,5,6 and tumorinfiltrating overall T-lymphocytes (oTL) inhibit tumor growth in colorectal and ovarian cancers. [7][8][9][10] Also, increased CD3 mRNA levels in the tumor correlate with improved outcome. 11 The function of regulatory T cells (Treg) is converse to the role of effector T-lymphocytes.…”

Section: Tumor Cells Express Specific Antigens Thus Becoming Targetsmentioning

confidence: 97%

“…7,8 CD25 + FOXP3 + cells show upregulation in tumor tissues. 17 Low levels of CD25 + CD4 + FOXP3 + cells 9 and high levels of CD3 mRNA 11 have been associated with better survival of cancer patients.…”

confidence: 98%

Epigenetic quantification of tumor-infiltrating T-lymphocytes

Sehouli¹,

Loddenkemper²,

Cornu³

et al. 2011

Epigenetics

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Analysis of the T Cell Receptor Variability of Tumor-Infiltrating Lymphocytes in Colorectal Carcinomas

Cited by 28 publications

References 16 publications

Coordination of Intratumoral Immune Reaction and Human Colorectal Cancer Recurrence

Coordination of Intratumoral Immune Reaction and Human Colorectal Cancer Recurrence

Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis

Epigenetic quantification of tumor-infiltrating T-lymphocytes

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