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T Lymphocytes Expressing Th1 Cytokines Selectively Accumulate in Human Colorectal Carcinoma

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  2. T Lymphocytes Expressing Th1 Cytokines Selectively Accumulate in Human Colorectal Carcinoma
  3. A Map of Smoking and Global Cancer Mortality
  4. Combining Weapons in the Fight Against Gliomas

Musha et al., pp. 949–956

T cell infiltration is often observed in human cancer tissues, in particular in colon cancer. Such infiltrates are generally associated with a favorable prognosis, probably because they reflect the presence of a certain degree of anti-tumor immunity. In particular, intra-epithelial CD8+ T cells represent an independent favorable prognostic factor in colorectal cancer tissues. In their study, Musha and colleagues characterized infiltrating lymphocytes in 40 cases of human colorectal cancer. Using immunohistochemistry, they observed an accumulation of T cells expressing CCR5 and CXCR3, a marker of Th1 lymphocytes, mainly along the invasive margin of the tumors. Using flow cytometry, they also observed that more than half of CD8+ T cells isolated from such tissues express CCR5 and CXCR3 at their surface and produced interferon γ over interleukin 4 in response to in vitro stimulation, in agreement with their Th1 phenotype. The ligand for CCR5, called RANTES/CCL5, was expressed in CD8+ T cells whereas the ligand for CXCR3, called IP-10/CXCL10, was mainly observed in macrophages and in cancer cells along the invasive margin. These observations are consistent with the selective recruitment of Th1 lymphocytes secreting interferon γ at the invasive margin of colorectal cancer and provide an explanation for their association with a favorable prognosis.

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Illustration 1. Immunohistochemistry of chemokine receptors: CCR5 and CXCR3 staining. Low (panels C & D) and high magnification (panels E & F) of cancer tissue (Ca) are shown. Arrows indicate cells staining positive for these two chemokine receptors at the invasive margin.

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A Map of Smoking and Global Cancer Mortality

  1. Top of page
  2. T Lymphocytes Expressing Th1 Cytokines Selectively Accumulate in Human Colorectal Carcinoma
  3. A Map of Smoking and Global Cancer Mortality
  4. Combining Weapons in the Fight Against Gliomas

Ezzati et al., pp. 963–971

Tobacco smoking remains the most widespread source of carcinogens in the world. An estimated 1.1 billion people smoke worldwide, most of them in industrialized countries. Smoking has been associated with at least 15 types of cancer, most importantly lung and upper aerodigestive tract cancers, but also cancers of the bladder, stomach and liver. Background risks for these smoking-related cancers vary greatly among epidemiologic subregions of the world because of socioeconomic, cultural and environmental differences.

This issue features a detailed analysis of the global and regional cancer mortalities caused by smoking. Ezzati and colleagues based their analysis on consistently adjusted hazards obtained from databases of the American Cancer Society, the World Health Organization and the International Agency for Research on Cancer. They calculated that in the year 2000 1.42 million cancer deaths or 21% of all global cancer deaths were caused by smoking. The regions with the largest number of smoking-related cancer deaths were the industrialized regions of western Europe (27% of all cancer deaths) and North America (34% of all cancer deaths). Lung cancer was the leading cause of smoking-related deaths in nearly all regions, but its contribution varied from 30 to 40% in Subsaharan Africa and parts of the Mediterranean region to 60–70% in North America and Europe. Cancer mortality caused by smoking was larger among men than among women, with 79% of smoking-related deaths among men in industrialized and 88% in developing countries. This extensive analysis confirmed that smoking is a major determinant of cancer mortality among men in all regions in the world.

Combining Weapons in the Fight Against Gliomas

  1. Top of page
  2. T Lymphocytes Expressing Th1 Cytokines Selectively Accumulate in Human Colorectal Carcinoma
  3. A Map of Smoking and Global Cancer Mortality
  4. Combining Weapons in the Fight Against Gliomas

Meng et al., pp. 992–997

Radiotherapy is a standard treatment for high-grade gliomas. In addition, clinical trials are underway to test the efficacy of oligodeoxynucleotides containing CpG motifs (CpG-ODN) as a potential treatment for patients with recurrent glioblastomas. CpG-ODNs are potent immunostimulatory agents that activate the innate and antigen-specific immune response through the Toll-like receptor 9. CpG-ODNs are usually injected at the tumor site and are thought to induce a tumor-specific immune response that extends to distant metastases.

A new study from the Hôpital de la Salpétrière in Paris shows that these two strategies, established radiotherapy and experimental treatment with CpG-ODN, can be successfully combined. Fisher rats implanted with 9L glioma cells were treated with radiotherapy, CpG-ODN or combinations of the two. Meng and colleagues chose a specific oligonucleotide (CpG-28) containing 3 CpG motifs with potent immunostimulatory effects in murine cells. Injection of CpG-28 into established 9L gliomas induced complete remission and long-term survival in 37% of rats, while none of the rats that received saline or a control CpG-ODN survived. The same survival rate was observed in rats treated with radiotherapy (33%). However, the combination of CpG-ODN and radiotherapy, even at low doses (10 Gy), resulted in a dramatic increase in survival (70%). This increase was only observed when these treatments were administered in close temporal association (<3 days), suggesting synergistic actions of the two treatments.