NKG2D+CD4+ T Cells with Immune Suppressive Property Increase in Patients with Colorectal Cancer

Some studies suggest that small populations of CD4+ T cells with activation-independent, constitutive, NKG2D expression are found in normal peripheral blood and have immune suppressive properties. The present study was designed to investigate NKG2D expression on CD4+ T lymphocytes and its relationship to immune evasion in colorectal cancer patients. We examined NKG2D expression on both circulating and tumor infiltrating CD4+ and CD8+ T cells or NK cells and evaluated it by multicolor flow cytometry. Furthermore, intracellular cytokine staining was carried out to determine the cytokine profile of NKG2D+CD4+ T cells in colorectal cancer patients. As a result, NKG2D expression on circulating and tumor-infiltrating CD8+ T cells and NK cells was downregulated in colorectal cancer patients. On the other hand, circulating and tumor-infiltrating NKG2D+CD4+ T cells increased in colorectal cancer patients. NKG2D+CD4+ T cells produced more immune suppressive cytokines, such as interleukin-10 and transforming growth factor-1β, than did NKG2D-CD4+ T cells. Increased NKG2D+CD4+ T cells as well as decreased NKG2D expression on CD8+ T cells and NK cells may be one of the key mechanisms responsible for immune evasion by tumors in colorectal cancer

Topoisomerase I Protein Expression and Prognosis of Patients with Colorectal Cancer

Topoisomerase I (Topo I) is known as a target for chemotherapy in advanced or recurrent colorectal cancer. In order to prolong the survival of patients with colorectal cancer or to prevent ineffective chemotherapy, we evaluated clinicopathological characteristics of Topo I protein in colorectal cancer. Also, we estimated whether Topo I protein expression of primary tumors could be a parameter for chemosensitivity of Topo I inhibitor in patients with cancer recurrence. Immunohistochemical detection of Topo I protein was performed in 104 surgically obtained specimens. Topo I protein was detected in 45 of 104 patients (43.2%). Topo I protein expression closely correlated with tumor progression, histpathological differentiation and poor prognosis of patients. Sixteen patients with recurrent cancer had been treated with Topo I inhibitor. Topo I inhibitor significantly prolonged the survival of 12 patients who had Topo I-positive primary tumors. Topo I protein expression in colorectal cancer may be a biological marker for chemosensitivity of tumors against Topo I inhibitors

Multicenter safety study of mFOLFOX6 for unresectable advanced/recurrent colorectal cancer in elderly patients

<p>Abstract</p> <p>Background</p> <p>Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) has become a standard regimen for colorectal cancer. An increase of adverse events with combination chemotherapy is predicted in elderly patients, and it remains controversial whether they should receive the same chemotherapy as younger patients. Accordingly, this study of modified FOLFOX6 (mFOLFOX6) therapy was performed to compare its safety between elderly and non-elderly patients.</p> <p>Methods</p> <p>We prospectively studies 14 non-elderly patients aged <70 years old and 8 elderly patients aged ≥ 70 years with unresectable advanced/recurrent colorectal cancer who received mFOLFOX6 therapy during the period from March 2006 to March 2007. Adverse events and the response to treatment were compared between the elderly and non-elderly groups.</p> <p>Results</p> <p>The main adverse events were neutropenia and peripheral neuropathy, which occurred in 62.5% (≥ grade 3) and 87.5% (≥ grade 1) of elderly patients. The grade and frequency of adverse events were similar in the elderly and non-elderly groups. In some patients with neutropenia, treatment could be continued without reducing the dose of oxaliplatin by deleting bolus 5-fluorouracil. A correlation was found between the cumulative dose of oxaliplatin and the severity of neuropathy, and there were 2 elderly and 3 younger patients in whom discontinuation of treatment was necessary due to peripheral neuropathy. The median number of treatment cycles was 10.0 and 9.5 in the non-elderly and elderly groups, respectively. The response rate was 60.0% in the non-elderly and 50.0% in the elderly group, while the disease control rate was 100% and 83.3% respectively, showing no age-related difference.</p> <p>Conclusion</p> <p>mFOLFOX6 therapy was well-tolerated and effective in both non-elderly and elderly patients. However, discontinuation of treatment was sometimes necessary due to peripheral neuropathy, which is dose-limiting toxicity of this therapy.</p

Multicenter Analysis of mFOLFOX6 with Oxaliplatin Stop-and-Go Strategy Using Oral Uracil-Tegafur with Leucovorin for Unresectable Colorectal Cancer in Elderly Patients

International audience(Civ. 3e, 12 juin 1991, Bull. civ. III, n° 173, p. 102 ; Defrénois 1991, p. 1014, obs. H. Souleau.