Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Work in animal models has suggested that interactions of members of the B7 receptor family (e.g., B7-1, B7-2) on tumor cells with their ligands CD28 and CTLA-4 on cytotoxic T cells (CTL) are important for the induction of anti-tumor immunity against malignant melanoma (MM). To determine whether these molecules are of relevance for CTL responses against human MM, we studied the expression of B7-1, B7-2, CD28 and CTLA-4 in primary tumors of MM (PMM), MM metastases (MMM) and benign melanocytic nevi (BMN) by immunohistochemistry (IH) and by reverse transcription polymerase chain reaction (RT-PCR). By RT-PCR, B7-1 and B7-2-specific mRNAs were detected in most PMM, MMM and BMN. These PCR-signals were derived from CD45(+)-infiltrating leukocytes and not from tumor cells since (I) MMM depleted of CD45+ cells contained no B7-1 or B7-2 mRNA; and (2) by IH, B7-1 and B7-2 were found on infiltrating dendritic cells, macrophages and a variable proportion of tumor-infiltrating lymphocytes (TIL) but not on melanoma cells or nevus cells. The important exceptions were 5/5 spontaneously regressing PMM, in which B7-1 and B7-2 were expressed by melanoma cells, that were surrounded by TIL expressing CD28 but not CTLA-4. We conclude that, in PMM, MMM and BMN, the majority of TIL are CD28+ and that B7-1 and B7-2 are expressed by CD45(+)-infiltrating antigen-presenting cells (APC) and TIL, but not by the tumor cells. However, in spontaneously regressing PMM, melanoma cells express B7-1, B7-2 and MHC class-I and -II antigens, particularly in areas with clinical and histological signs of an ongoing anti-tumor response. These data suggest that the absence of B7-1 and B7-2 favors the escape of MM from immunosurveillance, while B7-1, B7-2 expression enhances T-cell-mediated anti-tumor immunity.
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PMID:In situ expression of B7 and CD28 receptor families in human malignant melanoma: relevance for T-cell-mediated anti-tumor immunity. 754 78

Ipilimumab blocks cytotoxic T-lymphocyte-associated antigen (CTLA)-4, potentiating the antimelanoma T-cell host response. Ipilimumab has been shown to improve overall survival in patients with previously treated metastatic melanoma. CTLA-4 antibodies generate immune responses to the melanoma-associated antigens Melan-A, NY-ESO-1 and glycoprotein (gp)100 in metastatic melanoma. Digital epiluminescence microscopy (DELM) is a noninvasive method permitting the monitoring of the morphology of melanocytic lesions over time. A 50-year-old man with metastatic melanoma received four ipilimumab injections after failure of dacarbazine chemotherapy. Positron emission tomography revealed regression of pulmonary metastases, and simultaneously, DELM showed regression of several melanocytic naevi. On histological examination of the regressing naevi, prominent CD8+, CD4+ and CD45R0 lichenoid lymphohistiocytic infiltrates were seen, whereas nonregressing naevi were almost free of inflammatory infiltrate. Expression of melanoma-associated antigens in benign melanocytic naevi may explain the induction of naevus regression by ipilimumab. DELM could represent a valuable noninvasive method to monitor ipilimumab efficacy.
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PMID:Ipilimumab induces simultaneous regression of melanocytic naevi and melanoma metastases. 2302 81

Immunotherapy-induced vitiligo is an immune-related adverse event (irAE) observed in metastatic melanoma patients treated with immune checkpoint inhibitors that target the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) pathways. To date, the development of leukoderma, poliosis, and halo nevi during immunotherapy has largely been reported in metastatic melanoma patients. We report a case of immunotherapy-induced leukoderma presenting as halo nevi in a patient with non-small cell lung cancer (NSCLC) treated with atezolizumab, a programmed cell death ligand (PD-L1) antibody. Immunotherapy-induced vitiligo in metastatic melanoma patients may be associated with improved survival, but it remains to be determined whether its occurrence in non-melanoma cancers has the same prognostic significance. <p><em>J Drugs Dermatol. 2017;16(10):1047-1049.</em></p>.
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PMID:Development of Halo Nevi in a Lung Cancer Patient: A Novel Immune-Related Cutaneous Event from Atezolizumab. 2903 61