Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI-ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI-ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2−27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively ( p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7-73.8%).ICI-ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.This article has supplementary material available from

In recent years, significant progress has been made in the understanding of the pathophysiological mechanisms of acne and the role of Propionibacterium acnes. With this review, the authors aim to provide an update on the current understanding of the role of P. acnes in the development of acne lesions and analysing the potential implications for future treatments. A total of 188 articles published between January 1980 and March 2013 were searched using key words such as acne, P. acnes, microbiology, Corynebacterium acnes, acne vulgaris, pathogenesis, antibiotic, vaccination and a combination of those key words. From those articles, 77 were analysed in depth. Recent data confirm that P. acnes has a strong proinflammatory activity and targets molecules involved in the innate cutaneous immunity, keratinocytes and sebaceous glands of the pilosebaceous follicle and leads to the development of comedones. Furthermore, the profile of its different strains may differ between healthy subjects and acne patients. The better understanding of the role of P. acnes may allow for new perspectives in the treatment of acne. Novel therapies should target molecules implicated in the activation of innate immunity, including toll-like receptors, protease-activated receptors and topical antimicrobial peptides; the latter may be an alternative to topical antibiotics and thus a solution for limiting bacterial resistance induced by topical macrolides. Vaccines may also be promising. However, the most appropriate candidate remains to be selected.

Even though melanoma is considered to be one of the most immunogenic solid tumors, handling its development remains a challenge. The basis for such escape from antitumor immune control has not yet been documented. Plasmacytoid dendritic cells (pDC) are emerging as crucial but still enigmatic cells in cancer. In melanoma, the function of tumor-infiltrating pDCs remains poorly explored. We investigated the pathophysiologic role of pDCs in melanoma, both ex vivo from a large cohort of melanoma patients and in vivo in melanoma-bearing humanized mice. pDCs were found in high proportions in cutaneous melanoma and tumor-draining lymph nodes, yet associated with poor clinical outcome. We showed that pDCs migrating to the tumor microenvironment displayed particular features, subsequently promoting proinflammatory Th2 and regulatory immune profiles through OX40L and ICOSL expression. Elevated frequencies of interleukin (IL)-5-, IL-13-and IL-10-producing T cells in patients with melanoma correlated with high proportions of OX40L-and ICOSL-expressing pDCs. Strikingly TARC/CCL17, MDC/CCL22, and MMP-2 found in the melanoma microenvironment were associated with pDC accumulation, OX40L and ICOSL modulation, and/or early relapse. Thus, melanoma actively exploits pDC plasticity to promote its progression. By identifying novel insights into the mechanism of hijacking of immunity by melanoma, our study exposes potential for new therapeutic opportunities. Cancer Immunol Res; 1(6); 402-15. Ó2013 AACR.

This is the largest population-based study aiming to estimate the prevalence of five chronic skin inflammatory diseases.

Background: Cutibacterium acnes has been identified as one of the main triggers of acne. However, increasing knowledge of the human skin microbiome raises questions about the role of other skin commensals, such as Staphylococcus epidermidis, in the physiopathology of this skin disease. Summary: This review provides an overview of current knowledge of the potential role of S. epidermidis in the physiopathology of acne. Recent research indicates that acne might be the result of an unbalanced equilibrium between C. acnes and S. epidermidis,according to dedicated interactions. Current treatments act on C. acnesonly. Other treatment options may be considered, such as probiotics derived from S. epidermidis to restore the naturally balanced microbiota or through targeting the regulation of the host’s AMP mediators. Key Messages: Research seems to confirm the beneficial role of S. epidermidis in acne by limiting C. acnes over-colonisation and inflammation.

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Dendritic cells (DCs) are central cells in the development of antitumor immune responses, but the number and function of these cells can be altered in various cancers. Whether these cells are affected during the development of melanoma is not known. We investigated the presence, phenotype, and functionality of circulating myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) in newly diagnosed melanoma patients, compared to controls. The frequencies of PDCs and MDCs were equivalent in melanoma patients as compared with normal subjects. Both circulating DC subsets were immature, but on ex vivo stimulation with R848 they efficiently upregulated their expression of costimulatory molecules. We found that circulating DCs from melanoma patients and controls displayed similar pattern of expression of the chemokine receptors CXCR3, CXCR4, CCR7, and CCR10. Strikingly, PDCs from melanoma patients expressed higher levels of CCR6 than control PDCs, and were able to migrate toward CCL20. Further data showed that CCR6-expressing PDCs were present in melanoma primary lesions, and that CCL20 was produced in melanoma tumors. These results suggest that PDCs and MDCs are functional in melanoma patients at the time of diagnosis, and that CCL20 may participate to their recruitment from the blood to the tumor.

BackgroundThe development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs) in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy.Methods and FindingsStimulation of PBMC from HLA-A*0201+ donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer+ CD8 T cells). The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment.ConclusionsThese findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.