Mucosal-associated invariant T (MAIT) cells IntroductionMainstream T cells display a very diverse repertoire of antigen receptors, which enable these cells to respond to a wide variety of antigens presented by polymorphic major histocompatibility complex (MHC) molecules. During development, interactions between the T cells and selecting MHC class II and I molecules on thymic epithelial cells lead to the specific features of CD4 and CD8 T-cell lineage. However, 2 "innate-like" T lymphocytes, the natural killer T (NKT) and mucosal-associated invariant T (MAIT) cells, follow different ontogenic pathways with selection by nonpolymorphic MHC class Ib molecules. 1 Human MAIT cells express the semi-invariant T-cell receptor (TCR; iV␣7.2-J␣33) and are selected by the MHC class Ib molecule, MR1 on hematopoietic cells, which confer peculiar features. 2,3 Indeed, MAIT cells are enriched in the intestinal lamina propria and are numerous in the peripheral blood of healthy subjects. They are present in cord blood in small numbers with a naive phenotype, whereas in adults they represent approximately 10% of mature CD8 or CD4 Ϫ CD8 Ϫ (DN) T cells and display an effector-memory phenotype. We recently showed that MAIT cells specifically react against antigen-presenting cells (APCs), fed with a wide variety of bacteria and yeasts but not viruses, and display protective activity in experimental bacterial infection models. 4,5 In humans, they are defined as CD161 hi IL-18R␣ ϩ V␣7.2 ϩ ␥␦ Ϫ CD3 ϩ lymphocytes. 3,4 Either CD161 or IL-18R␣ expression at the cell surface, together with the V␣7.2 segment, allows for the unequivocal identification of MAIT cells in both peripheral blood and tissues. 3,4 CD161 (KLRB1, NKRP1A) is a C-type lectin family member, part of the NK complex. 6 Ligands for CD161 have been described only recently, and blocking or cross-linking CD161 may modulate T-cell functions. 7-9 CD161 is also expressed by the majority of NK cells and diverse subsets of T lymphocytes that include TCR-␥␦ T cells and most NKT cells. CD161 expression is found on a significant proportion of tissue-infiltrating T cells, such as the intestine and liver. [10][11][12] The frequency of these cells varies in certain pathologic conditions, such as cancer and viral or autoimmune diseases. [12][13][14][15] Recently, it has been demonstrated that a subset of naive cord blood CD4 T cells express CD161 and are precursors of peripheral, mature, Th17 T cells. 16 CD161 expression seems to correlate with interleukin-17 (IL-17) secretion by CD4 T cells. 17 Among TCR-␣␤ T cells, most of the CD161 ϩ T cells belong to the CD4 subset. However, CD8 T cells expressing CD161 can also be found, but their nature has just begun to be explored. CD161 ϩ CD8 T cells can be split into 2 different populations expressing intermediate or high levels of CD161. Two recent reports independently raised new findings on this latter subset. The first shows that CD161 hi CD8 T cells represent self-renewing memory cells, which survive chemotherapy. 18 These cells are absent from...

This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs.

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been recently investigated in several cancer types, but their respective clinical significance remains to be determined. In our prospective study, we compared the detection rate and the prognostic value of these two circulating biomarkers in patients with metastatic uveal melanoma. GNAQ=GNA11 mutations were characterized in archived tumor tissue. Using a highly sensitive and mutation-specific bidirectional pyrophosphorolysisactivated polymerization (bi-PAP) technique, GNAQ c.626A>T, GNAQ c.626A>C and GNA11 c.626A>T copy numbers were quantified in plasma from 12 mL of blood. CTCs were detected at the same time in 7.5 mL of blood by the CellSearchV R technique. Patient characteristics and outcome were prospectively collected. CTCs (1) were detected in 12 of the 40 included patients (30%, range 1-20). Among the 26 patients with known detectable mutations, ctDNA was detected and quantified in 22 (84%, range 4-11,421 copies=mL). CTC count and ctDNA levels were associated with the presence of miliary hepatic metastasis (p 5 0.004 and 0.03, respectively), with metastasis volume (p 5 0.005 and 0.004) and with each other (p < 0.0001). CTC count and ctDNA levels were both strongly associated with progression-free survival (p 5 0.003 and 0.001) and overall survival (p 5 0.0009 and <0.0001). In multivariate analyses, ctDNA appeared to be a better prognostic marker than CTC. In conclusion, ctDNA and CTC are correlated and both have poor prognostic significance. CTC detection can be performed in every patient but, in patients with detectable mutations, ctDNA was more frequently detected than CTC and has possibly more prognostic value.Uveal melanoma is a rare cancer, with a reported incidence of two to eight new cases per million per year in Europe 1 and the United States.2 Specific mutations are found in this particular type of melanoma: >80% of uveal melanoma express mutually exclusive somatic mutations in two paralog proto-oncogenes, GNAQ 3 and GNA11, 4 which encode a-subunits of heterotrimeric G-proteins involved in the MEK-ERK signaling pathway. 5 In both genes, most mutations occur at nucleotide 626 encoding a glutamine at codon 209 (Q209). The presence of these mutations does not influence the risk of metastasis in patients. 4 Uveal melanoma metastases develop mostly in the liver through hematogenous spread of cancer cells. Despite improvement of diagnosis and treatment of the primary eye tumor, there is no effective treatment of metastatic disease; the prognosis of patients with metastatic uveal melanoma is limited, and although a few patients experience extended survival, the median overall survival (OS) following metastases detection is less than 1 year. 6 Circulating tumor cells (CTCs), which are cancer cells detected in patient blood, may correspond to cancer "seeds" that initiate metastatic relapse.7 Over the past two decades, both molecular and cytological detection techniques have

This large human study provides valuable information about MAIT cells in severe bacterial infections. The persistent depletion of MAIT cells is associated with the further development of ICU-acquired infections.