Therapeutic reduction of cell-mediated immunosuppression in mycosis fungoides and S ézary syndrome
AbstractTumor progression is associated with progressive immunosuppression mediated in part by T regulatory cell(s) (Treg) and/or myeloid-derived suppressor cell(s) (MDSC). Development of strategies to reduce populations of immune cells with suppressive function in cancer patients may enable the induction or recovery of immunity against tumor cells, which may limit or reverse disease progression. With a goal of developing Treg and MDSC neutralizing strategies to treat mycosis fungoides (MF) and S ézary syndrome (SzS), we determined the association between disease stage and suppressor cell populations in patients with MF/SzS, including those responding to therapy. We found elevations in Treg populations, across Treg subtypes, in patients with SzS, and these Treg markedly suppressed prolifera tion of autologous CD4+CD25− responder T cells. Interestingly, while MDSC numbers were not increased in MF/SzS patients, MDSC from patients with stage IB and above produced significantly more reactive oxygen species than those from stage IA MF patients and control cohorts. Therapy with the CD25-targeting agent denileukin diftitox or IFN- α2b was associated with a reduction in Treg numbers or MDSC function, respectively. These studies identify potential mechanisms of action for these therapies and support the development of coordinated strategies targeting both Treg and MDSC activities in patients with MF/SzS.
In conclusion, cdTSE has a limited role in SS. TTNT is reduced in heavily pre-treated MF patients, suggesting greater benefit when utilized earlier in treatment sequencing.
Abstract Most patients with mycosis fungoides are diagnosed with early-stage disease. However, prevalence of early-stage disease is unknown, and evidence of its burden is scarce. The aim of this study is to estimate the prevalence of early-stage mycosis fungoides, how long patients live with early-stage disease and to characterise these patients. Data were obtained from 4 key publications and from US cancer registries (Surveillance, Epidemiology and End Results Program; SEER). The derived incidence of early-stage mycosis fungoides was 0.26/100,000 (UK), 0.29/100,000 (US) and 0.38/100,000 (US-SEER) and the prevalen...
CONCLUSIONS: These findings demonstrate that LDRT can eradicate malignant T cells in MF, provides robust disease control, and is associated with improved survival in high-risk early stage patients. PMID: 31636100 [PubMed - as supplied by publisher]
Abstract Mogamulizumab, approved by the FDA for relapsed or refractory mycosis fungoides and Sézary syndrome, improves progression-free survival compared to vorinostat in the largest trial to date in cutaneous T-cell lymphoma, with particular efficacy in leukemic disease, but carries a risk of immune-mediated toxicities with concomitant depletion of regulatory T-cells. PMID: 31615932 [PubMed - as supplied by publisher]
ConclusionTSEBT improved disease symptoms and significantly improved emotional domains of patients ’ quality of life in patients with MF or SS. In addition, our results indicate that maintenance or adjuvant therapy after TSEBT may improve the PFS.
Publication date: Available online 20 September 2019Source: Seminars in Cancer BiologyAuthor(s): Hermann A.M. MuckeABSTRACTIntellectual property documents (patents and their published applications) are not only collections of legal exclusivity claims but also repositories of scientific and technical information, even though they are not peer reviewed. We have identified and analyzed international disclosures concerning drug repurposing for cancer that were published under the Patent Convention Treaty during the past five years, and show this burgeoning field from an angle that is not routinely captured in review papers of ...
The molecular weight of methotrexate (MTX) makes cutaneous penetration difficult. Oxygen flow could enhance the skin permeation of MTX diluted in the LP3 carrier system. This pilot study aims to assess the efficacy, safety and tolerance of oxygen-flow-administered (OFA)-LP3-MTX3% for treating superficial skin cancers. Patients with superficial basal cell carcinoma (sBCC)(n=12), extramammary Paget ’s disease (EMPD)(n=5), mycosis fungoides classic type (CMF) (n=10) and folliculotropic (FMF) (n=6) were included in the study and were treated with 4 weekly applications of OFA-LP3-MTX3%.
The prevalence of mycosis fungoides / S ézary syndrome (MF/SS) is higher in the African American (AA)/black population compared to Caucasians in the United States and worse outcomes have been observed in AA/black patients.
Clinical and laboratory diagnostics of mycosis fungoides (MF), the most common cutaneous lymphoma is challenging. Our previous work described 4 promising markers of S ézary syndrome (SS): T-plastin, Twist, NKp46 and KIR3DL2 (Michel et al. 2013). Tox has been shown to be an additional marker for MF and SS. The aim of the present study was to confirm this combination of blood-derived markers in a validation cohort of SS, erythodermic and earlier MF for improving d iagnosis and predicting prognosis. Patients with a confirmed diagnosis of MF or SS and patients with other skin diseases were included.
We examined the relationship between nitrogen mustard (NM)-induced lymphomatoid papulosis (LyP) in patients with mycosis fungoides (MF). Nine patients were included who were initially diagnosed with MF and subsequently developed LyP in the setting of NM induced inflammation. The average time from initiation of NM therapy to development of LyP was 5.2 months. The majority of patients presented to their follow-up visit with new red bumps, most commonly located on the buttocks/lower extremities, with symptoms of pain and pruritus in 6/9 patients.