<scp>SSX2</scp>‐4 expression in early‐stage non‐small cell lung cancer

Greve, Katrine Buch Vidén; Pøhl, Mette; Olsen, Karen Ege; Nielsen, Ole; Ditzel, Henrik J.; Gjerstorff, Morten F.

doi:10.1111/tan.12340

Cited by 17 publications

(17 citation statements)

References 30 publications

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“…Previous studies show that HCT116 do not express NY-ESO-1 and SSX-2 proteins (24)(25)(26)(27). In our current study, we confirmed that cancer-specific CTLs did induce IFNg and TNFa in cocultures with HCT116 cells in the absence of external peptide loading (Supplementary Fig.…”

Section: Discussionsupporting

confidence: 88%

“…Prior to culturing, target cells were externally loaded with corresponding peptides (SSX-2 or NY-ESO-1, 10 mg/mL) at 37 C for 1 hour to enable the loading and presentation of the peptides on the MHC complex on the target cell surface. HCT116 is a commercially available cancer cell line that is known to be HLA-A2 þ , E-Cadherin þ (the ligand for CD103) and does not express SSX-2 and NY-ESO-1 proteins (24)(25)(26)(27). Another condition was also included by using THP-1 as target cells, which is E-Cadherin -HLA-A2 þ SSX-2 -NY-ESO-1 -.…”

Section: Target Cell Lines Used For In Vitro Functional Assaysmentioning

confidence: 99%

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Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses

Hamid

Colin‐York

Alham

et al. 2020

Cancer Immunology Research

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Enrichment of CD103 þ tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103 þ cytotoxic CD8 þ T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103 þ CTLs by assessing T-cell receptor (TCR)-matched CD103 þ and CD103cancer-specific CTL immunity in vitro and its immunophenotype ex vivo. Interestingly, we found that differentiated CD103 þ cancer-specific CTLs expressed the active form of TGFb1 to continually self-regulate CD103 expression, without relying on external TGFb1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103 þ CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103 þ cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies.

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Section: Discussionsupporting

confidence: 88%

Section: Target Cell Lines Used For In Vitro Functional Assaysmentioning

confidence: 99%

Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses

Hamid

Colin‐York

Alham

et al. 2020

Cancer Immunology Research

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“…The Synovial Sarcoma, X-breakpoint (SSX) family comprises six highly similar members with additional splicing variants (i.e., SSX1, SSX2, SSX3, SSX4, SSX5 and SSX7) and several pseudogenes [75]. The proteins are strictly expressed in the spermatogonia of testis in healthy individuals, but ectopic expression is found in many different types of human cancer [76,77]. The proteins are most frequently detected in melanoma, where approximately 40% of tumors are positive for SSX2, SSX3 or SSX4 [78].…”

Section: The Ssx Family Of Chromatin-modulating Proteinsmentioning

confidence: 99%

Interaction between Polycomb and SSX Proteins in Pericentromeric Heterochromatin Function and Its Implication in Cancer

Johansen

Gjerstorff

2020

Cells

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The stability of pericentromeric heterochromatin is maintained by repressive epigenetic control mechanisms, and failure to maintain this stability may cause severe diseases such as immune deficiency and cancer. Thus, deeper insight into the epigenetic regulation and deregulation of pericentromeric heterochromatin is of high priority. We and others have recently demonstrated that pericentromeric heterochromatin domains are often epigenetically reprogrammed by Polycomb proteins in premalignant and malignant cells to form large subnuclear structures known as Polycomb bodies. This may affect the regulation and stability of pericentromeric heterochromatin domains and/or the distribution of Polycomb factors to support tumorigeneses. Importantly, Polycomb bodies in cancer cells may be targeted by the cancer/testis-related SSX proteins to cause derepression and genomic instability of pericentromeric heterochromatin. This review will discuss the interplay between SSX and Polycomb factors in the repression and stability of pericentromeric heterochromatin and its possible implications for tumor biology.

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“…SSX proteins are germ cell-specific proteins that are expressed at the spermatogonial stage of spermatogenesis 11 . They are also ectopically expressed in many types of tumors, such as 40% of melanomas and up to 65% of breast cancers 12,13 . The SSX family comprise nine highly identical members, which are most likely redundant in their cellular functions 14 .…”

Section: Introductionmentioning

confidence: 99%

A functional genetic screen identifies the Mediator complex as essential for SSX2-induced senescence

et al. 2019

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The senescence response to oncogenes is believed to be a barrier to oncogenic transformation in premalignant lesions, and describing the mechanisms by which tumor cells evade this response is important for early diagnosis and treatment. The male germ cell-associated protein SSX2 is ectopically expressed in many types of cancer and is functionally involved in regulating chromatin structure and supporting cell proliferation. Similar to many wellcharacterized oncogenes, SSX2 has the ability to induce senescence in cells. In this study, we performed a functional genetic screen to identify proteins implicated in SSX2-induced senescence and identified several subunits of the Mediator complex, which is central in regulating RNA polymerase-mediated transcription. Further experiments showed that reduced levels of MED1, MED4, and MED14 perturbed the development of senescence in SSX2expressing cells. In contrast, knockdown of MED1 did not prevent development of B-Raf-and Epirubicin-induced senescence, suggesting that Mediator may be specifically linked to the cellular functions of SSX2 that may lead to development of senescence or be central in a SSX2-specific senescence response. Indeed, immunostaining of melanoma tumors, which often express SSX proteins, exhibited altered levels of MED1 compared to benign nevi. Similarly, RNA-seq analysis suggested that MED1, MED4, and MED14 were downregulated in some tumors, while upregulated in others. In conclusion, our study reveals the Mediator complex as essential for SSX2-induced senescence and suggests that changes in Mediator activity could be instrumental for tumorigenesis.

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SSX2‐4 expression in early‐stage non‐small cell lung cancer

Cited by 17 publications

References 30 publications

Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses

Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses

Interaction between Polycomb and SSX Proteins in Pericentromeric Heterochromatin Function and Its Implication in Cancer

A functional genetic screen identifies the Mediator complex as essential for SSX2-induced senescence

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