The bone marrow represents an enrichment site of specific T lymphocytes against filamentous fungi

Bone marrow has already been described as an enrichment site for several antigen-specific T lymphocytes, but the presence of mould-specific T cells has never been investigated in the bone marrow. We have previously demonstrated that mould-specific T cells emerge in the peripheral blood of patients with invasive fungal infections (IFI) but tend to become undetectable after disease resolution. In seven patients with a history of IFI, we investigated the presence of mould-specific T cells secreting different cytokines in bone marrow and peripheral blood paired samples. The results showed that the frequencies of mould-specific T cells secreting the protective cytokine IFNI3 are significantly higher in bone marrow (BM) and are mainly represented by CD8+ T lymphocytes with effector phenotype. A putative disappearance of such protective BM responses after myeloablative therapy could contribute to the increased risk of IFI in hematologic patients

Prognostic Relevance of Multi-Antigenic Myeloma-Specific T-Cell Assay in Patients with Monoclonal Gammopathies

: Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies

Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia

Nucleophosmin(NPM1)-mutated protein, a leukemia-specific antigen, represents an ideal target for AML immunotherapy. We investigated the dynamics of NPM1-mutated-specific T cells on PB and BM samples, collected from 31 adult NPM1-mutated AML patients throughout the disease course, and stimulated with mixtures of 18 short and long peptides (9-18mers), deriving from the complete C-terminal of the NPM1-mutated protein. Two 9-mer peptides, namely LAVEEVSLR and AVEEVSLRK (13.9-14.9), were identified as the most immunogenic epitopes. IFNγ-producing NPM1-mutated-specific T cells were observed by ELISPOT assay after stimulation with peptides 13.9-14.9 in 43/85 (50.6%) PB and 34/80 (42.5%) BM samples. An inverse correlation between MRD kinetics and anti-leukemic specific T cells was observed. Cytokine Secretion Assays allowed to predominantly and respectively identify Effector Memory and Central Memory T cells among IFNγ-producing and IL2-producing T cells. Moreover, NPM1-mutated-specific CTLs against primary leukemic blasts or PHA-blasts pulsed with different peptide pools could be expanded ex vivo from NPM1-mutated AML patients or primed in healthy donors. We describe the spontaneous appearance and persistence of NPM1-mutated-specific T cells, which may contribute to the maintenance of long-lasting remissions. Future studies are warranted to investigate the potential role of both autologous and allogeneic adoptive immunotherapy in NPM1-mutated AML patients

Cutaneous melanoma metastatic to uterine adenomyoma: report of a case

Rare cases of metastasis to uterine polyps have been reported in English literature but not, to the best of our knowledge, to uterine adenomyomas. All these cases are represented by breast cancer, most of them involving tamoxifen-associated polyps. We first report a case of cutaneous malignant melanoma metastatic to uterine adenomyoma. A computed tomography scan did not reveal any further evidence of disease, suggesting that this metastatic localization may represent something more than a fortuitous case. Based on these observations it is suggested that a subset of malignant melanoma and breast cancer cells share a sort of homing'' phenomenon to polypoid lesions of uterus, due probably to the presence of some chemokines and their specific receptors. Pathologists should be aware of this possibility in order to look carefully for metastatic implants in similar lesions. It is proposed that chemokine profile of neoplastic cells can be a useful tool in predicting metastatic targets

MRI and correlation between TNM and CEA, CA19.9, AFP in rectal cancer Experience of a single academic surgical center

In our study we examined 75 patients treated for rectal cancer in the period between 01/01/2011 and 31/12/2014. Out of these 75 patients, we considered those 36 staged through MRI. We then compared the TNM stage obtained through MRI with the one emerged from histological examination. The correlation between the two TNM stages was assessed considering all patients staged through MRI and dividing the cases according to the submission or not to a neoadjuvant treatment. Finally, we analyzed serum levels of tumor markers CEA, CA 19.9 and AFP, relating them with the final disease stage. Data analysis showed a statistically significant correlation in the T stages, especially in the population not subjected to neoadjuvant treatment. Instead, for N, we found no statistically significant correlation. Similarly, none of the tumor markers presented a statistically significant correlation with disease stage. However, according to the positivity of tumor markers, we associated the following score: 0, (no positive marker)1 (only one marker positive) 2 (two markers positive) 3 (three markers positive). In presence of three markers positive, meaning the highest score, we found a statistically significant correlation with N + staging of the disease, obtained by postoperative pathologic examination. The conclusion is that MRI is certainly effective in T stage evaluation. Probably, for limph node involvement evaluation, more reliable parameters for establishing possible lymph node malignancy need to be found. The role of the tumor markers CEA, CA 19.9, AFP during preoperative evaluation of rectal tumors remains undefined. KEY WORDS: MRI, Rectal cancer, Tumor markes, Tumor regression, T stage

Characterization of the (Poly)Phenolic Fraction of Fig Peel: Comparison among Twelve Cultivars Harvested in Tuscany

(1) Background: The fig tree (Ficus carica L.) is widely cultivated in the Mediterranean area and it produces fruits largely consumed in the Mediterranean diet. Previous studies have shown that this fruit represents a rich source of (poly)phenols, which are mainly located in the peel rather than the pulp. In our study, fig peel derived from twelve different cultivars located in Tuscany was assessed for its (poly)phenol profile. (2) Methods: The (poly)phenol characterization was performed through ultra-high performance liquid chromatography coupled to multiple-stage mass spectrometry. (3) Results: Twenty-eight (poly)phenolic compounds were quantified in the investigated fig peel. It was possible to observe an interesting variability in the (poly)phenol content among the twelve cultivars of fig peel. Rutin and 5-caffeoylquinic acid were the main compounds in the greenish fig peel, while cyanidin-3-O-rutinoside was the main component in the dark-violet fig peel. (4) Conclusions: fig peel could be used as a (poly)phenol-rich ingredient in several food products to increase the bioactive compound content of foods. Moreover, dark-violet peel could be considered potentially suitable as a natural food colorant