T helper 22 cells from Han Chinese patients with atopic dermatitis exhibit high expression of inducible T‐cell costimulator

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L–OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L–OX40 axis as a promising target for the treatment of atopic dermatitis.

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Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan

Scientific Reports ◽

10.1038/s41598-021-88289-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Abram Bunya Kamiza ◽

Wen-Chang Wang ◽

Jeng-Fu You ◽

Reiping Tang ◽

Huei-Tzu Chien ◽

...

Keyword(s):

Colorectal Cancer ◽

Lynch Syndrome ◽

Cumulative Risk ◽

Germline Mutations ◽

Han Chinese ◽

Chinese Patients ◽

Mutation Carriers ◽

Amsterdam Criteria ◽

Cumulative Risks ◽

Age And Sex

AbstractPatients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

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Remission of Alopecia Universalis after 1 Year of Treatment with Dupilumab in a Patient with Severe Atopic Dermatitis

Skin Appendage Disorders ◽

10.1159/000517832 ◽

2021 ◽

pp. 1-4

Author(s):

Maurizio Romagnuolo ◽

Mauro Barbareschi ◽

Simona Tavecchio ◽

Luisa Angileri ◽

Silvia Mariel Ferrucci

Keyword(s):

Atopic Dermatitis ◽

Skin Disorder ◽

Human Monoclonal Antibody ◽

Severe Atopic Dermatitis ◽

T Helper ◽

T Helper 1 ◽

Th2 Response ◽

Alopecia Universalis ◽

T Helper 2 ◽

Relapsing Remitting

Alopecia areata (AA), an autoimmune disease with a relapsing-remitting course, represents the second cause of nonscarring alopecia worldwide and is associated with several comorbidities, notably atopic dermatitis (AD). In particular, AD is related to its more severe forms alopecia totalis (AT) and alopecia universalis (AU) [Nat Rev Dis Primers. 2017;3:17011]. Considering that AA has been classified as T helper 1-driven disease, whereas AD is the prototypical T helper 2 (Th2)-driven skin disorder, recent studies suggest that these forms may underlie a different chemokine expression resulting in a Th2 skewing as a key pathomechanism that could explain this association [JAMA Dermatol. 2015 May;151(5):522–8]. Several reports showed that dupilumab, a fully human monoclonal antibody targeting the interleukin 4α receptor and thus downregulating Th2 response, led to an improvement of AA associated with AD; most of these patients were females with AT or AU, early-onset AD, and atopic comorbidities [Exp Dermatol. 2020 Aug;29(8):726–32]. We report here a case to further support this hypothesis.

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PTEN loss correlates with T cell exclusion across human cancers

BMC Cancer ◽

10.1186/s12885-021-08114-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ziying Lin ◽

Lixia Huang ◽

Shao Li Li ◽

Jincui Gu ◽

Xiaoxian Cui ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Helper Cells ◽

Pi3k Pathway ◽

T Helper ◽

Immune Microenvironment ◽

Pten Loss ◽

Pathway Activation ◽

Tumor Types ◽

T Cell Exclusion

Abstract Background Recent evidences had shown that loss in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was associated with immunotherapy resistance, which may be attributed to the non-T-cell-inflamed tumor microenvironment. The impact of PTEN loss on tumor microenvironment, especially regarding T cell infiltration across tumor types is not well understood. Methods Utilizing The Cancer Genome Atlas (TCGA) and publicly available dataset of immunotherapy, we explored the correlation of PTEN expressing level or genomic loss with tumor immune microenvironment and response to immunotherapy. We further investigated the involvement of PI3K-AKT-mTOR pathway activation, which is known to be the subsequent effect of PTEN loss, in the immune microenvironment modulation. Results We reveal that PTEN mRNA expression is significantly positively correlated with CD4/CD8A gene expression and T cells infiltration especially T helpers cells, central memory T cell and effector memory T cells in multiples tumor types. Genomic loss of PTEN is associated with reduced CD8+ T cells, type 1 T helper cells, and increased type 2 T helper cells, immunosuppressed genes (e.g. VEGFA) expression. Furthermore, T cell exclusive phenotype is also observed in tumor with PI3K pathway activation or genomic gain in PIK3CA or PIK3CB. PTEN loss and PI3K pathway activation correlate with immunosuppressive microenvironment, especially in terms of T cell exclusion. PTEN loss predict poor therapeutic response and worse survival outcome in patients receiving immunotherapy. Conclusion These data brings insight into the role of PTEN loss in T cell exclusion and immunotherapy resistance, and inspires further research on immune modulating strategy to augment immunotherapy.

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