Gonococcal keratoconjunctivitis in adults JS Lee et al 646Eye her knees and loose-jointedness. Her vision was 6/4 bilaterally, without any angioid streaks. His son had stiff joints except his knees, extensible skin over the neck and face and a normal ocular examination. It was felt that our case was a PXE heterozygote and that angioid streaks were part of this clinical phenotype. In the absence of cutaneous changes homozygosity for the PXE gene is unlikely, although it cannot be totally excluded. DNA has been extracted and banked to test for the PXE gene in the future. A formal skin biopsy from the side of the neck showed minimal elastotic degeneration and elastic fibres were not Von Kossa positive. There were no particular features suggestive of PXE. The recent normal colonoscopy rules out Familial Adenomatous Polyposis (FAP). CommentCongenital hypertrophy of the retinal pigment epithelium (CHRPE) is a well-known association of Familial Adenomatous Polyposis (FAP). On reviewing literature there is one case report of a middle-aged Caucasian male with angioid streaks but no CHRPE who had extensive FAP. 4 The relationship between CHRPE and angioid streaks is probably coincidental and has not been reported before. The previously reported case had extensive FAP necessitating a total colectomy, though his fundi did not show any features of CHRPE. Both these patients were Caucasian males, of similar age and with radiological evidence of degenerative changes in their lumbar vertebrae. The striking similarity between these cases and the fact that CHRPE and FAP often are part of the same syndrome suggests that their relationship with angioid streaks could be part of the same syndrome. In the present case the cutaneous manifestations of PXE were minimal, while in the previously reported case FAP was not associated with CHRPE, possibly indicating an incomplete expression. References

Background Transforming growth factor beta (TGF-β) is a typical immuno-inhibitory cytokine and highly secreted by lung cancer cells. It was supposed that its immunosuppressive effects to NK cell might be related with the altered expression of activating and inhibitory molecules in lung cancer cells. In this study, we examined the expression of NKG2DLs, PD-L1 and PD-L2 in lung cancer cells after treatment of TGF-β and a TGF-β inhibitor, Galunisertib (LY2157299). Results TGF-β reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-β on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-β, it was thought that TGF-β induced the expression of MMP2 which facilitated the shedding of the NKG2DLs in cancer cells. However, the expression of PD-L1, L2 were not changed by treatment with TGF-β or Galunisertib. Conclusions Therefore, inhibition of TGF-β might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.

Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.

Background Since ionizing radiation has showed the dramatic effect to kill the cancer cells by direct DNA damage as well as triggering anti-cancer immune responses through release of various tumor antigens and induction of NK activating molecules, it has been used for long time to treat many cancer patients including patients with melanoma. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system. One of the suggested ways is induction of a ligand for programmed death-1 (PD-L1) after radiotherapy in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity in T cells. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1/2 in malignant melanoma cells and the receptor, PD-1, in NK-92 cells. Results Surface PD-L1/2 levels on melanoma cells were increased by ionizing radiation in a dose-dependent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1/2 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1/2+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene to inhibit PD-1/PD-L1 axis, they reversed the activity of the suppressed NK cells. Conclusions Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.