Given the close interaction between tumor cells and stromal cells in the tumor microenvironment (TME), TME-targeted strategies would be promising for developing integrated cancer immunotherapy. Cancer-associated fibroblasts (CAFs) are the dominant stromal component, playing critical roles in generation of the pro-tumorigenic TME. We focused on the immunosuppressive trait of CAFs, and systematically explored the alteration of tumor-associated immune responses by CAF-targeted therapy. C57BL/6 mice s.c. bearing syngeneic E.G7 lymphoma, LLC1 Lewis lung cancer, or B16F1 melanoma were treated with an anti-fibrotic agent, tranilast, to inhibit CAF function. The infiltration of immune suppressor cell types, including regulatory T cells and myeloid-derived suppressor cells, in the TME was effectively decreased through reduction of stromal cell-derived factor-1, prostaglandin E2, and transforming growth factor-β. In tumor-draining lymph nodes, these immune suppressor cell types were significantly decreased, leading to activation of tumor-associated antigen-specific CD8+ T cells. In addition, CAF-targeted therapy synergistically enhanced multiple types of systemic antitumor immune responses such as the cytotoxic CD8+ T cell response, natural killer activity, and antitumor humoral immunity in combination with dendritic cell-based vaccines; however, the suppressive effect on tumor growth was not observed in tumor-bearing SCID mice. These data indicate that systemic antitumor immune responses by various immunologic cell types are required to bring out the efficacy of CAF-targeted therapy, and these effects are enhanced when combined with effector-stimulatory immunotherapy such as dendritic cell-based vaccines. Our mouse model provides a novel rationale with TME-targeted strategy for the development of cell-based cancer immunotherapy.

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Cancer-associated fibroblasts (CAFs) are the dominant stromal component in the tumour microenvironment (TME), playing critical roles in generation of protumourigenic TME; however, their contribution to suppression of antitumour immune responses has not been fully understood. To elucidate the interaction between CAFs and immune suppressor cells, we examined whether inhibition of CAFs function would impair the induction of immune suppressor cell types in vitro. In this study, we applied an anti-allergic and antifibrotic agent tranilast, which is used clinically, and evaluated a potential of tranilast to serve as a CAFs inhibitor. CAFs that had been isolated from E.G7 or LLC1 tumour-bearing mice were cultured in the presence of tranilast, and thereafter, CAFs functions on the secretion of some soluble factors as well as the induction of immune suppressor cells were evaluated. As a result, tranilast inhibited the proliferation of CAFs and reduced the levels of stromal cell-derived factor-1, prostaglandin E 2 and transforming growth factor-b1 from CAFs in a dose-dependent manner. On the other hand, tranilast exerted no inhibitory effects on immune cells at doses under 100 lM. The induction of regulatory T cells and myeloid-derived suppressor cells from their progenitor cells was suppressed in the medium that CAFs had been cultured in the presence of tranilast; however, these findings were not observed when those progenitor cells were cultured in the medium containing tranilast alone. These data demonstrate that tranilast inhibits CAFs function, which is responsible for the induction of immune suppressor cells, and possesses a potential to serve as a specific CAFs inhibitor.

Background: Lung cancer patients frequently suffer from sarcopenia, and reports on the association of resectable lung cancer and their postoperative outcomes are increasing. Information on whether sarcopenia has any impact on short-and long-term postoperative outcomes in patients surgically treated for nonsmall cell lung cancer remains insufficient. Furthermore, reports vary regarding the pathological stage, surgical procedure, diagnostic tool of sarcopenia, cut-off value, prognosis, and postoperative complications.We believe that sarcopenia assessment should be included as one of the factors which affect the surgical outcomes of lung cancer. Thus, we conducted a review and meta-analysis to ascertain the association between sarcopenia and postoperative outcomes. Methods: We performed a systematic literature search in PubMed/MEDLINE. Studies included cases defined sarcopenia, received lung cancer surgery, assessed postoperative complications, and prognosis. The pooled odds ratios for survival and postoperative complications, with 95% confidence intervals, were generated using Review manager 5.3. Results: A total of ten retrospective studies were eligible for this meta-analysis, including a total of 2,643 non-small cell lung cancer patients. All reviews used skeletal muscle mass as a diagnostic tool for sarcopenia.Sarcopenia was associated with worse survival outcomes and increased postoperative complications in patients with resected lung cancer. Conclusions: Sarcopenia is an independent risk factor for postoperative death and postoperative complications in patients who have undergone surgery. It is necessary to explore the mechanism of sarcopenia and optimal intervention, such as exercise, nutrition, or drug therapy.

A diagnosis of thoracic endometriosis is simple when both endometrial stroma and gland are present. In cases of endometriosis with stroma only, a further classification of "aggregated pattern", in which immunohistochemistry is ER-, PR- and CD10-positive might be necessary for diagnosis.

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The proposed risk score was able to predict the incidence of postoperative complications. The risk score can be used to identify high-risk patients and to select proper treatment strategies.