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IgA + B cells expressing programmed death ligand 1 (PD-L1) and interleukin 10 accumulate in the inflamed livers of humans and mice with non-alcoholic fatty liver disease where they promote the progression to hepatocellular carcinoma by limiting the local activation of PD-1-expressing CD8 + T cells. The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA + ) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8 + T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8 + T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA + cell generation attenuates liver carcinogenesis and induces cytotoxic T-lymphocyte-mediated regression of established hepatocellular carcinoma. These findings establish the importance of inflammation-induced suppression of cytotoxic CD8 + T-lymphocyte activation as a tumour-promoting mechanism. Increased cancer risk in fatty livers Cancer progression beyond the early stages is thought to be caused in some cases by adaptive immunity, but its role remains controversial. In this study, Michael Karin and colleagues show that PD-L1-expressing IgA + B cells accumulate in the inflamed livers of humans and mice with non-alcoholic fatty liver disease. The inflammation-induced IgA + cells promote the progression to hepatocellular carcinoma by suppressing liver cytotoxic CD8 + T cells that prevent the emergence of this aggressive tumour.

In this Article, the sentence: “After 7 months of HFD, MUP-uPA mice developed HCC 15 , which contained numerous (usually 50–100 per tumour) non-recurrent coding mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).”, should have read: “After 7 months of HFD, MUP-uPA mice developed HCC 15 , which contained numerous (usually 50–100 per tumour) non-recurrent mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).”. This has been corrected online. In Extended Data Fig. 6a and b, which show the number of point mutations identified per sample and the mutational signatures, all sequence variants (including non-coding mutations) are shown. Fig. 2d also presents all variants compared to human mutations. In the Supplementary Information to this Amendment, we now provide the comparisons of all variants and coding variants to human mutations.

Nature 551, 340–345 (2017); doi:10.1038/nature24302 In this Article, owing to an error during the production process, the text ‘(Iga is also known as Cd79a)’ was erroneously added to the sentence describing the generation of MUP-uPA/Iga−/− and STAM/Iga−/− mice; this should have stated ‘(Iga is also known as Igha)’.

Phyllodes tumors (PT) are rare fibroepithelial neoplasms of the breast that are predominantly benign, but can exhibit malignant characteristics. Elevated beta-human chorionic gonadotropin (beta-hCG) levels, primarily associated with pregnancy and trophoblastic tumors, have been rarely reported in breast cancers and PT. We present a 28-year-old premenopausal female with a rapidly growing, painful mass in the right breast. Imaging and biopsy confirmed a malignant PT. Surprisingly, preoperative testing revealed a positive urine pregnancy test (UPT) and an elevated beta-hCG level (1,152.7 mlU/mL). After pregnancy was deemed unlikely, the patient proceeded with a right total mastectomy. Postoperatively, the beta-hCG level decreased, confirming tumor-related phenomenon. Pathology revealed malignant PT with liposarcomatous components and ductal carcinoma in situ (DCIS). The association between PT and elevated beta-hCG levels is exceptionally rare and poorly understood. This case highlights the importance of considering unusual presentations in PT patients.

In this Article, the sentence: \"After 7 months of HFD, MUP-uPA mice developed HCC.sup.15, which contained numerous (usually 50-100 per tumour) non-recurrent coding mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).\", should have read: \"After 7 months of HFD, MUP-uPA mice developed HCC.sup.15, which contained numerous (usually 50-100 per tumour) non-recurrent mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).\". This has been corrected online. In Extended Data Fig. 6a and b, which show the number of point mutations identified per sample and the mutational signatures, all sequence variants (including non-coding mutations) are shown. Fig. 2d also presents all variants compared to human mutations. In the Supplementary Information to this Amendment, we now provide the comparisons of all variants and coding variants to human mutations.

The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA+) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8+ T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8+ T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA+ cell generation attenuates liver carcinogenesis and induces cytotoxic T-lymphocyte-mediated regression of established hepatocellular carcinoma. These findings establish the importance of inflammation-induced suppression of cytotoxic CD8+ T-lymphocyte activation as a tumour-promoting mechanism.