Immune activation status of CD8+ T cells infiltrating non-small cell lung cancer

Trojan, Andreas; Urosevic, Mirjana; Dummer, Reinhard; Giger, Robin; Weder, Walter; Stahel, Rolf A.

doi:10.1016/j.lungcan.2003.11.004

Cited by 44 publications

(32 citation statements)

References 27 publications

(29 reference statements)

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“…Our demonstration of a regulatory role for CD8 ϩ T cells in the lung is also consistent with studies on non-small cell lung cancer, which demonstrated low concentrations of IFN-␥ and elevated IL-10 and TGF-␤ at the tumor site (23) and high numbers of tumor-infiltrating CD8 ϩ T cells, which did not correlate to patient survival (24). CD8…”

Section: Depletion Of Cd8supporting

confidence: 89%

Suppression of Antitumor Immunity by IL-10 and TGF-β-Producing T Cells Infiltrating the Growing Tumor: Influence of Tumor Environment on the Induction of CD4+ and CD8+ Regulatory T Cells

Jarnicki

Lysaght

Todryk

et al. 2006

The Journal of Immunology

378

260

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We examined the hypothesis that a failure of the immune system to eradicate tumors is due to the immunosuppressive environment created by the growing tumor, which is influenced by the site of tumor growth. We demonstrated that T cell responses to a bystander Ag in mice were suppressed by a growing CT26 tumor. T cells purified from the growing tumor expressed mRNA for IL-10, TGF-β, and Foxp3. Intracellular cytokine staining revealed a high frequency of IL-10-secreting macrophages, dendritic cells, and CD4+ and CD8+ T cells infiltrating the tumor. In contrast, T cell IFN-γ production was weak and CD8+ CTL responses were undetectable in mice with CT26 lung metastases and weak and transient following s.c. injection of CT26 cells, but were enhanced in the presence of anti-IL-10 and anti-TGF-β. Consistent with this, removal of CD8+ T cells abrogated CTL responses and promoted progression of the s.c. tumor. However, in the lung model, depletion of CD8+ T cells significantly reduced the tumor burden. Furthermore, depletion of CD4+ or CD25+ T cells in vivo reduced tumor burden in s.c. and lung models, and this was associated with significantly enhanced IFN-γ production by CD8+ T cells. These findings suggest that tumor growth facilitates the induction or recruitment of CD4+ regulatory T cells that secrete IL-10 and TGF-β and suppress effector CD8+ T cell responses. However, CD8+ T regulatory cells expressing IL-10 and TGF-β are also recruited or activated by the immunosuppressive environment of the lung, where they may suppress the induction of antitumor immunity.

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Section: Depletion Of Cd8supporting

confidence: 89%

Suppression of Antitumor Immunity by IL-10 and TGF-β-Producing T Cells Infiltrating the Growing Tumor: Influence of Tumor Environment on the Induction of CD4+ and CD8+ Regulatory T Cells

Jarnicki

Lysaght

Todryk

et al. 2006

The Journal of Immunology

378

260

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“…Examining the functional significance of CD8þ T cells, Trojan and colleagues analyzed the mRNA ratio of IFN-g to CD8, in which IFN-g is an effector cytokine secreted by cytotoxic T cells, specifically in peritumoral areas and within tumor nests. Although the number of peritumoral CD8þ T cells correlated with the IFN-g/CD8 ratio, this association was not observed intratumorally (8). This study suggests that, whereas the CD8þ T cells are able to infiltrate the tumor, they are not able to mount a robust antitumor response once within the tumor nest.…”

Section: Tumor-infiltrating Lymphocytesmentioning

confidence: 62%

“…Among T lymphocytes, which comprise 80% of tumorinfiltrating lymphocytes (TIL) in NSCLC (5), CD8þ cytotoxic lymphocytes form the effector arm of adaptive immunity and are thought to have protective roles against tumors. However, 5 investigations in NSCLC show no correlation between CD8þ TIL infiltration and survival (6)(7)(8)(9)(10). Pertinent to NSCLC patients is the fact that CD8þ T-cell predominance is a characteristic of smoking-related chronic obstructive pulmonary disease (11), and it is thought to drive the progression of emphysema (12).…”

Section: Tumor-infiltrating Lymphocytesmentioning

confidence: 99%

Prognostic Immune Markers in Non–Small Cell Lung Cancer

Suzuki

Kachala

Kadota

et al. 2011

Clinical Cancer Research

150

104

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Tumor-associated immune responses have polarized effects in regulating tumor growth. Although a clear association has been shown between the tumor immune response and clinical outcome in colorectal and ovarian cancers, the role of immune markers for stratifying prognosis in non-small cell lung cancer (NSCLC) is less defined. Herein, we review the prognostic significance of published immune markers in the tumor microenvironment and peripheral blood of NSCLC patients. To identify prognostic immune genes, we reviewed all published gene-profiling studies in NSCLC and delineated the significance of immune genes by doing subanalysis on the microarray database of the NIH Director's Challenge study. This first comprehensive review of prognostic immune markers provides a foundation for further investigating immune responses in NSCLC.

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“…In stage IV NSCLC patients with chemotherapy, CD8 + T cells in cancer nest link to a favorable outcome, 19 but some other studies suggested that they could not demonstrate an influence on survival of lung adenocarcinoma patients. 20–22 A recent study using in silico analysis of tumor immunity also underpinned this conclusion, when taking patient age and stage into consideration. 23 …”

Section: Discussionmentioning

confidence: 89%

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

et al. 2018

OncoImmunology

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Tobacco smoking causes DNA damages in epithelial cells and immune dysfunction in the lung, which collectively contribute to lung carcinogenesis and progression. However, potential mechanisms by which tumor-infiltrating immune cells contribute to lung cancer survival and their differential contributions in ever-smokers and never-smokers are not well studied. Here, we performed integrative analysis of 11 lung cancer gene-expression datasets, including 1,111 lung adenocarcinomas and 200 adjacent normal lung samples. Distinct pathways were altered in lung carcinogenesis in ever-smokers and never-smokers. Never-smoker patients had a better outcome than ever-smoker patients. We characterized compositional patterns of 21 types of immune cells in lung adenocarcinomas and revealed the complex association between immune cell composition and clinical outcomes. Interestingly, we found two subsets of immune cells, mast cells and CD4+ memory T cells, which had completely opposite associations with outcomes in resting and activated status. We further discovered that several chemokines and their associated receptors (e.g., CXCL11-CX3CR1 axis) were selectively altered in lung tumors in response to cigarette smoking and their abundances showed stronger correlation with fractions of these immune subsets in ever-smokers than never-smokers. The status switched from the resting to activated forms in mast cells and CD4+ memory T cells might manifest some important processes induced by cigarette smoking during tumor development and progression. Our findings suggested that aberrant activation of mast cells and CD4+ memory T cells plays crucial roles in cigarette smoking-induced immune dysfunction in the lung, which contributes to tumor development and progression.

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Immune activation status of CD8+ T cells infiltrating non-small cell lung cancer

Cited by 44 publications

References 27 publications

Suppression of Antitumor Immunity by IL-10 and TGF-β-Producing T Cells Infiltrating the Growing Tumor: Influence of Tumor Environment on the Induction of CD4+ and CD8+ Regulatory T Cells

Suppression of Antitumor Immunity by IL-10 and TGF-β-Producing T Cells Infiltrating the Growing Tumor: Influence of Tumor Environment on the Induction of CD4+ and CD8+ Regulatory T Cells

Prognostic Immune Markers in Non–Small Cell Lung Cancer

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments

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