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Primary localized cutaneous amyloidosis (PLCA) is a rare form of cutaneous amyloidosis, characterized by the presence of flat-topped papules and macules with amyloid deposits in the superficial dermis. It is a purely cutaneous disease with no association with systemic forms of amyloidosis.1 Although most cases are sporadic, familial cases (FPLCA) represent about 10% of total reports and show an autosomal dominant inheritance, with mutations described in the genes for the oncostatin M receptor (OSMR) and the interleukin-31 receptor A (IL31RA).2 Herein, we present a family affected by FPLCA and underline the role of caspase activation in amyloid formation.

Background Target antigen (Ag) loss has emerged as a major cause of relapse after chimeric antigen receptor T (CART)-cell therapy. We reasoned that the combination of CART cells, with the consequent tumor debulking and release of Ags, together with an immunomodulatory agent, such as the stimulator of interferon gene ligand (STING-L) 2 ' 3 '-cyclic GMP-AMP (2 ' 3 '-cGAMP), may facilitate the activation of an endogenous response to secondary tumor Ags able to counteract this tumor escape mechanism. Methods Mice bearing B16-derived tumors expressing prostate-specific membrane Ag or gp75 were treated systemically with cognate CART cells followed by intratumoral injections of 2 ' 3 '-cGAMP. We studied the target Ag inmunoediting by CART cells and the effect of the CART/STING-L combination on the control of STING-L-treated and STING-L-non-treated tumors and on the endogenous antitumor T-cell response. The role of Batf3-dependent dendritic cells (DCs), stimulator of interferon gene (STING) signaling and perforin (Perf)-mediated killing in the efficacy of the combination were analyzed. Results Using an immune-competent solid tumor model, we showed that CART cells led to the emergence of tumor cells that lose the target Ag, recreating the cancer immunoediting effect of CART-cell therapy.