Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunotherapy has emerged as a potent approach for treating aggressive cancers, such as non-small-cell lung tumors and metastatic melanoma. Clinical trials are now in progress for patients with malignant gliomas; however, a better understanding of how these tumors escape immune surveillance is required to enhance antitumor immune responses. With gliomas, the recruitment of CD8+ T cells to the tumor is impaired, in part preventing containment or elimination of the tumor. In this issue of the JCI, Kohanbash and colleagues present an elegant dissection of how gliomas exploit an enzymatic activity acquired through a common mutation to abrogate the migration of CD8+ T cells to the tumor. They show that the oncometabolite 2-hydroxyglutarate (2HG), generated by mutated forms of isocitrate dehydrogenase (IDH1 and IDH2), reduces the expression of STAT1, thereby limiting the production of the chemokines CXCL9 and CXCL10. As a result, IDH1-mutated tumors are less effectively infiltrated by CD8+ T cells, contributing to tumor escape. Finally, in mice harboring syngeneic gliomas, an inhibitor of 2HG synthesis complemented vaccination to ameliorate tumor control. Understanding how to increase immune infiltration of gliomas represents a key first step in achieving tumor destruction through immunotherapy.
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PMID:Resisting fatal attraction: a glioma oncometabolite prevents CD8+ T cell recruitment. 2831 49

Immunohistochemistry is an essential component of diagnostic breast pathology. The emergence of novel assays and applications is accompanied by new interpretation criteria and potential pitfalls. Immunohistochemistry assists in supporting breast origin for primary or metastatic carcinomas and identifying non-mammary metastases to the breast; however, no single immunostain is perfectly sensitive nor specific. GATA3 and Sox10 are particularly useful immunostains to identify triple negative breast carcinoma, which are often negative for other markers of mammary differentiation. Sox10 labeling is a major potential diagnostic pitfall, as Sox10 and S-100 label both triple negative breast carcinoma and metastatic melanoma; a pan-cytokeratin immunostain should always be included for this differential diagnosis. Novel immunohistochemistry serves as surrogates for the molecular alterations unique to several of special-type breast carcinomas, including the use of MYB in adenoid cystic carcinoma, pan-TRK in secretory carcinoma, and mutant IDH2 in tall cell carcinoma with reversed polarity (TCCRP). In addition, PD-L1 immunohistochemistry is an emerging, albeit imperfect, biomarker for breast cancer immunotherapy, with different assay parameters and scoring criteria in breast carcinoma compared to other tumor types. The expanding repertoire of novel immunohistochemistry provides additional diagnostic tools and biomarkers that improve diagnostic breast pathology and patient care.
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PMID:Novel uses of immunohistochemistry in breast pathology: interpretation and pitfalls. 3311 Feb 39