Mucosal (MM) and acral melanomas (AM) are rare melanoma subtypes of unmet clinical need; 15%-20% harbor KIT mutations potentially targeted by small-molecule inhibitors, but none yet approved in melanoma. This multicenter, single-arm Phase II trial (NICAM) investigates nilotinib safety and activity in KIT mutated metastatic MM and AM. KIT mutations are identified in 39/219 screened patients (18%); of 29/39 treated, 26 are evaluable for primary analysis. Six patients were alive and progression free at 6 months (local radiology review, 25%); 5/26 (19%) had objective response at 12 weeks; median OS was 7.7 months; ddPCR assay correctly identifies KIT alterations in circulating tumor DNA (ctDNA) in 16/17 patients. Nilotinib is active in KIT-mutant AM and MM, comparable to other KIT inhibitors, with demonstrable activity in nonhotspot KIT mutations, supporting broadening of KIT evaluation in AM and MM. Our results endorse further investigations of nilotinib for the treatment of KIT-mutated melanoma. This clinical trial was registered with ISRCTN (ISRCTN39058880) and EudraCT (2009-012945-49).

Immune cell-driven anti-cancer activity is paramount for effective responses to checkpoint inhibitors (ICB). However, the contribution of the different immune cell subsets in the circulation and within the tumour is poorly understood. To elucidate the role of the different cell subsets in anti-tumour responses elicited by ICB, we performed single-cell analysis of the transcriptome and surface proteome of paired pre- and early on-treatment metastatic melanoma tumour biopsies and matched peripheral blood mononuclear cell samples. We next compared the survival of metastatic melanoma patients treated with ICB according to the abundance of pre-treatment tumour-infiltrating B cell clonotypes. We identified cell clusters associated with disease control or progression, defined differential expression of biological pathways likely involved in the immune awakening against the tumour and examined how cell-cell communication patterns between the tumour cell subsets change during treatment. Furthermore, we discovered that B cells (immunoglobulin expression and abundance of B cell clonotypes) discriminate the clinical response after ICB and propose that B cells likely contribute to anti-tumour immunity by antigen presentation through major histocompatibility complex molecules. Finally, we demonstrated that the abundance of tumour-infiltrating B cell clonotypes at baseline identifies two distinct risk groups, a finding that we confirmed in an independent cohort. Our exploratory translational study provides new insights on the mechanistic role of B cells in anti-melanoma immunity during treatment with ICB. Additionally, we support pre-treatment B cell tumour infiltration as a promising prognostic biomarker to be further validated as a tool for clinical risk stratification.

Background: The movement of endemic diseases from tropical and disadvantaged areas is gradually spreading to developed countries as well. Amoebiasis, in particular, represents a significant threat to public health, amplified by globalization and increasing contact between humans and animals or vectors. In this way, atypical diseases may emerge in our country, also through an unusual mode of transmission—likely sexual, as “sexually transmitted enteric (STE) diseases”. Objective: We report and discuss the clinic approach to a rare case of dual human infestations by ecto- and endo-parasites with multiple liver abscesses presentation in a young truck driver residing in Northern Italy. Methods: The patient underwent a comprehensive screening with laboratory and microbiological tests, and CT images. Results: In July, the patient was admitted to our hepatology unit following the ultrasound identification of two hypoechoic lesions in the right lobe of the liver. In his medical history, in April, after a seemingly harmless infestation of body lice, effectively treated, he suffered from a prolonged and debilitating episode of acute diarrhea, lasting a month. This status was also accompanied by intestinal cramps, weight loss, and recurring fever episodes. Afterwards also appeared a Quincke’s-like angioedema involving the lips and mouth mucosa, with evening time exacerbation. Conclusions: The differential diagnosis of this complex and unusual clinical picture, together with the temporal evolution of the patient’s signs and symptoms, led us to hypothesize the presence of concomitant infections. These were most likely borreliosis and a STE disease, the latter ultimately diagnosed as amebiasis with hepatic invasion, allowing appropriate treatment and a favorable clinical outcome.