PD-1: A Negative Regulator of Phagocytosis by Tumour-Associated Macrophages in Colon Cancer

Programmed cell death protein 1 (PD-1) is an immuno-inhibitory cell surface receptor protein of the myeloid, and lymphoid cell. PD-L1 is the ligand of PD-1, which is abundant in different malignant tissue e.g. skin, colon and breast cancer. PD-1/PD-L1 interaction helps the tumour cell to escape from the immune response by limiting TCR mediated T lymphocytes proliferation. Recently, PD-1 or PD-L1 blocking immunotherapy proved their efficacy in the treatment of different cancers. However, PD-1/PD-L1 interaction is well studied in T lymphocytes, but little is known about its function in tumour-associated macrophages (TAMs). In the tumour microenvironment, phagocytosis by TAMs plays a vital role in the immune response. In this review, the significance of PD-1 expression by TAMs and how it influences tumour immunity will be discussed. Recently, it has been found that PD-1 can express by TAMs and its expression level is directly related to duration and stages of colon cancer. TAMs expression of PD-1 was shown to be related to significant depletion of cancer cell phagocytosis. Monoclonal antibody against either PD-1 or PD-L1 in mice model of colon cancer promotes tumour cell phagocytosis by TAMs, thereby limiting the growth of the tumour and increase life expectancy. Therefore, PD-1 can be a promising target in macrophage-mediated immune therapy.

A Case of Cytophagic Histiocytic Panniculitis Involving the Extrapleural Fat / 대한피부과학회지

Cytophagic histiocytic panniculitis gap (CHP) was described in 1980 as a chronic histiocytic disease of the subcutaneous tissue and associated with systemic manifestations such as fever, serositis, and hepatosplenomegaly. The current concept of CHP is that it represents a spectrum of lymphoproliferative disorders that induce secondary histiocytic cytophagocytosis. The pathogenesis of hemophagocytosis in CHP is unknown but may be related to histiocyte reaction to an abnormal cytokine milieu brought about by disordered T-cell function. In most cases the disease follows a fulminant course, but in some patients the disease seems limited to the skin and subcutaneous tissue and follows a more benign, chronic course. We report a case of cytophagic histiocytic panniculitis which had a long chronic course over 16 years, but recently became aggravated with the involvement of the extrapleural fat tissue and was treated with combination chemotherapy.

A Case of Subcutaneous Panniculitic T-cell Lymphoma-like Lesion Occurring in a Patient with Systemic Lupus Erythematosus / 대한피부과학회지

Subcutaneous panniculitic T-cell lymphoma and lupus panniculitis may present histologic similarities, including lobular lymphocytic infiltrate, eosinophilic fat necrosis, histiocytic cytophagocytosis, lymphocytic angioinvasion and lymphocytic atypia. The observation that lupus panniculitis precedes or coincides with subcutaneous panniculitic T-cell lymphoma can make the diagnosis even more enigmatic. We describe a case of a 46-year old woman who presented with multiple infiltrative nodules on her arm. Her medical history of ongoing systemic lupus erythematosus favored a presumptive diagnosis of lupus panniculitis. However, the histopathologic examination, immunohistochemical study and T-cell receptor gene analysis revealed subcutaneous panniculitic T-cell lymphoma with hemophagocytic syndrome.

Effect of Inositol-phosphatase on Fc Receptor-mediated Phagocytosis of Macrophages

BACKGROUND: Fc receptor-mediated phagocytosis is a complex process involving the activation of kinases and phosphatases. FcgammaRIIB has been known to transduces inhibitory signals through an immunoreceptor tyrosine-based inhibitory motif (ITIM) in cytoplasmic domains. In this study, we examined the involvement of inositol-phosphatase in the Fc receptor-mediated phagocytosis. METHODS: J774 cells were infected using vaccinia viral vector containing SH2 domain-containing inositol-phosphatase (SHIP) cDNA and stimulated with the sensitized sheep red blood cells. RESULTS: Stimulation of J774 cells induced the tyrosine phosphorylation of SHIP which was maximal at 5 minutes. Phosphatidylinositol-3 (PI-3) kinase inhibitor (wortmannin) inhibits J774 cell phagocytosis of sensitized sheep red blood cells in a dose-dependent manner. Heterologious expression of SHIP in J774 cells inhibits phagocytosis of sensitized sheep red blood cells in a dose-dependency manner, but catalytically dead mutants of SHIP has no effect on phagocytosis. CONCLUSION: These results strongly suggest that the active signals mediated by PI-3 kinase are opposed by inhibitory signals through SHIP in the regulation of Fc receptor-mediated phagocytosis.

Two Cases of Cutaneous Rosai-Dorfman Disease / 대한피부과학회지

Rosai-Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy (SHML) is a benign, idiopathic histiocytic proliferative disorder affecting lymph nodes as well as extranodal sites. It is accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Although cutaneous involvement in RDD is common, a purely cutaneous disease is very rare. Histologic findings show characteristic large, pale, histiocytic cells exhibiting cytophagocytosis (emperipolesis). Immunohistochemically, these histiocytes are positive for S-100 protein and CD68, but negative for CD1a. The etiology is unknown, although it is thought to be a reactive disorder rather than neoplastic. We report two cases of Rosai-Dorfman disease showing involvement limited to the skin.

Cytologic Findings of Giant Cell Carcinoma of the Lung / 대한세포병리학회지

Pulmonary giant cell carcinoma is one of the most highly malignant neoplasms of the lung. Although mixed malignant glandular or squamous components may be associated with a giant cell carcinoma, it is a distinct clinical and morphologic entity. We reviewed cytologic presentations of 6 cases of pulmonary giant cell carcinoma. Cytologically, the single most characteristic feature of giant cell carcinoma was an extremely large, bizarre cancer cell engulfing numerous leukocytes. The nuclei of these cells showed occasional prominent nucleoli, and the cytoplasm was abundant. Giant cells were also seen in other types of pulmonary carcinoma, but the giant cells of this neoplasm could be differentiated from those encountered in undifferentiated large cell carcinoma and squamous cell carcinoma by the abundant cytoplasm, the presence of markedly enlarged nuclei, prominent nucleoli, and an significant degree of phagocytosis, In conclusion, precise diagnosis and classification of lung cancer is imperative because of proved correlation between cell type and prognosis.