T-cell Intracellular Antigen-1 Research Articles

Androgen Deprivation Boosts Prostatic Infiltration of Cytotoxic and Regulatory T Lymphocytes and Has No Effect on Disease-Free Survival in Prostate Cancer Patients

The value of neoadjuvant hormone therapy (NHT) prior to radical prostatectomy as a means of restraining prostate cancer (PCa) and strengthening its immunotherapy is still uncertain. This article asks whether it subverts immunoregulatory pathways governing tumor microenvironments, and has an impact on patient outcome. We microdissected epithelium and stroma from cancerous and normal prostate specimens from 126 prostatectomized patients, of whom 76 had received NHT, to detect cytokine/chemokine gene expression levels by real-time reverse transcriptase PCR. Confocal microscopy was used to identify cytokine/chemokine cell sources, and immunostainings to characterize lymphocyte subsets whose prognostic effects were assessed by Kaplan-Meier analyses. NHT boosted the expression of IL-7 in the stroma and that of IFNγ-inducible protein-10/CXCL10 in the glandular epithelium of normal prostate tissue, and restored the CD8(+) lymphocyte depletion occurring in PCa, whereas it significantly increased the CD4(+) lymphocyte infiltrate. Lymphocytes, mostly with CD8(+) phenotype, expressed the T-cell intracellular antigen-1, granzyme-B, and perforin, typical of cytotoxic-effector T cells. NHT also induced thymus and activation-regulated chemokine/CCL17 production by monocytes/macrophages in the prostate and draining lymph nodes, and increased the number of their Forkhead box P3 (Foxp3)(+)CD25(+)CD127(-) T regulatory (Treg) cells. The χ(2) test disclosed the lack of association (P = 0.27) between NHT and the high intratumoral CD8(+)/Treg ratio indicative of a good prognosis. Androgen withdrawal regulates cytokine/chemokine gene expression in normal prostate and lymphoid tissues, and this probably favors both CD8(+) and Treg infiltrates, leaves their intratumoral balance unchanged, and thus has no impact on disease-free survival.

Immunophenotypic characteristics and clinical relevance of CD56+ and CD56− extranodal nasal-type natural killer/T-cell lymphoma

This study aimed to determine whether the phenotypic characteristics of the two subtypes of CD56+ and CD56− lymphoma have relevance for their clinical behavior and prognosis. The immunophenotypes of all patients were confirmed using standard criteria for CD20, CD3ε, CD56, cytotoxic molecules (T-cell intracellular antigen-1 [TIA-1] and granzyme B), and Ki-67, and in situ hybridization for Epstein–Barr virus (EBV)-encoded RNA (EBER). CD56 was expressed in 90 of 118 (76.3%) patients. The majority (83.3%) of patients with nasal natural killer/T-cell lymphoma (NKTCL) presented with CD56+ lymphoma, whereas patients with NKTCL of the extranasal upper aerodigestive tract were more likely to have CD56− lymphoma (53.6%, p < 0.000). A lower percentage of expression of granzyme B and Ki-67 (>50%) was found in patients with CD56− lymphoma compared with those with CD56+ lymphoma (p < 0.05). The clinical characteristics and prognosis were comparable between patients with CD56+ and CD56− lymphomas. The corresponding overall survival and progression-free survival rates were 74.1% and 56.7%, respectively, for patients with CD56+ lymphoma compared with 81.6% and 60.5% for those with CD56− lymphoma (p > 0.05). There was no clinical or prognostic significance in determining the two subtypes of CD56+ and CD56− NKTCL based on their immunophenotypic profiles, which has clinical implications for pathological diagnosis and insight into disease behavior.

A Rapidly Regressing Wart Following Biopsy

Dear Editor: Warts are also known as verrucae, and these are benign proliferative lesions of the epidermis that are caused by human papilloma virus (HPV) infections1. There are many treatment modalities for warts, which implies that no single modality is uniformly effective. The choice of treatment depends on the location, size, number and type of wart, as well as on the patient's age and cooperation. Irrespective of the treatment modality, a host immune response is the key to achieving complete clearance. As such, immune-compromised individuals may never achieve wart clearance2. In other words, wart eradication can be achieved if the HPV-specific immunity can be stimulated. We report here on a case of a rapidly regressed wart following biopsy without any additional treatment. A 50-year-old woman presented to our clinic with a complaint of a papule located on her right cheek. The lesion was flesh to light brown in color and about 1 cm in diameter. It appeared more than 6 months prior to her presentation as a small pimple-like lesion, which had been slowly growing (Fig. 1A) without any associated pain or itching sensation. Its clinical appearance resembled seborrheic keratosis or other benign papules. A 2 mm-punch biopsy was taken at the center of the lesion without suturing. The histopathological findings were hyperkeratosis and papillomatosis, with elongated rete ridges and koilocytes. Immunohistochemical staining for CD3, CD4, CD8, CD20, CD56 and cytotoxic T cell intracellular antigen-1 (TIA-1) was performed. The dermal lymphocytes were predominantly CD3 and CD4-positive T-cells. The intraepidermal exocytotic cells were mildly positive for CD8 and TIA-1. The staining for CD20 and CD56 was negative. A diagnosis of wart was made. The lesion rapidly regressed within one week of the biopsy (Fig. 1B) and it had completely disappeared when the patient presented for follow-up after one month. Fig. 1 (A) Before biopsy; a flesh to light brown colored papule that was about 1 cm in diameter on the patient's right cheek (inset: close-up view). (B) One week later following biopsy, the wart had nearly disappeared, leaving only slight erythema (inset: close-up ... The role of immunity in HPV infection is not completely understood3,4. The decreasing trend of the prevalence of wart with age suggests that resistance to HPV infection develops over time, and much of this phenomenon may be immunological2. Individuals with impaired cell-mediated immunity are particularly susceptible to HPV infections, and these individuals' warts are recalcitrant to treatment5. There are instances in which treatment of one or more warts leads to complete clearance in immune-competent individuals. Children with warts may not require treatment since spontaneous regression is common as their immunity develop1. One report has suggested that specific cell-mediated immunity against viral infected keratinocytes took place in the process of spontaneous plane wart regression6. Another study demonstrated CD4-positive lymphocytes predominated in regressing genital wart7. Our case could also be interpreted in a similar context. Tissue biopsy might have exposed viral antigens to the host immune system, which subsequently triggered HPV-specific immunity. The immunohistochemical staining for TIA-1 was positive in the epidermis, which also means there was an activated cytotoxic T-cell infiltration. It is also possible that this patient had already developed HPV-specific cell-mediated immunity prior to the biopsy, and without the intervention the verruca could have remained as a solitary papule. The biopsy may have then exposed viral antigens and induced a delayed hypersensitivity reaction, which led to rapid regression of the lesion. A cutaneous wart management guideline has proposed curettage and light cautery for facial warts2. This was the similar course of action we took for our patient. There have been many cases of warts with spontaneous regression, but there has been no report of wart regression following a small biopsy. In conclusion, wart regression requires an immune reaction to viral antigens. Therefore, inducing and mounting such a response are critical for the management of warts.

TIAR and TIA-1 mRNA-Binding Proteins Co-aggregate under Conditions of Rapid Oxygen Decline and Extreme Hypoxia and Suppress the HIF-1 Pathway

T-cell intracellular antigen (TIA)-1 and TIA-1-related protein (TIAR) are mRNA-binding proteins that can aggregate within granules under specific stress conditions. In this study, we analyzed TIAR/TIA-1 aggregation under different hypoxic conditions, and studied the effects on the hypoxia-inducible factor (HIF)-1α in different cancer cell lines. Under acute and pronounced hypoxic conditions TIAR/TIA-1 co-aggregated to granules and positive co-staining with eIF3η marker suggested these to represent stress granules. In parallel, HIF-1α expression was blocked in cells displaying TIAR/TIA-1 granules. Silencing of TIAR and TIA-1 caused upregulation of HIF-1α expression, as demonstrated by western blot, immunocytochemistry and HIF-1-dependent reporter gene expression. Additionally, a critical region of the 3' end of the untranslated HIF-1α mRNA with possible adenosine-uridine-rich elements (AREs) was coupled to the luciferase reporter gene, causing downregulation of expression. Employing this reporter construct, inhibition of TIAR by siRNA attenuated the inhibitory cis-effect of this ARE-sequence. Furthermore, immunohistochemical analysis of A549 cell tumor xenografts revealed a nearly complementary expression of HIF-1α and TIAR reflecting the control of HIF-1α expression by TIAR as revealed in the cell culture studies. In sum, rapid and severe hypoxia caused co-aggregation of TIAR/TIA-1 and these proteins suppressed HIF-1α expression.

Cell-specific regulation of Fas exon 6 splicing mediated by Hu antigen R

The differential expression levels of T-cell intracellular antigens (TIA) and Hu antigen R (HuR) are concomitant with a splicing switch in apoptosis receptor Fas in HCT-116 cells. Thus, overexpression and knockdown of HuR led to Fas exon 6 skipping and inclusion, respectively. These results suggest that the TIA and HuR cellular ratio influences cell-type specific Fas exon 6 splicing pattern.

Heterogeneous ribonucleoprotein C displays a repressor activity mediated by T-cell intracellular antigen-1-related/like protein to modulate Fas exon 6 splicing through a mechanism involving Hu antigen R

T-cell intracellular antigen (TIA)-proteins are known regulators of alternative pre-mRNA splicing. In this study, pull-down experiments and mass spectrometry indicate that TIAR/TIAL1 and hnRNP C1/C2 are associated in HeLa nuclear extracts. Co-immunoprecipitation and GST-pull-down assays confirmed this interaction. Interestingly, binding requires the glutamine-rich (Q-rich) C-terminal domain of TIAR and the leucine-rich plus acidic residues-rich C-terminal domains of hnRNP C1/C2. This interaction also occurs in an RNA-dependent manner. Recombinant GFP-TIAR and RFP-hnRNP C1 proteins display partial nuclear co-localization when overexpressed in HeLa cells, and this requires the Q-rich domain of TIAR. hnRNP C1 overexpression in the presence of rate-limiting amounts of TIAR in HeLa and HEK293 cells affects alternative splicing of Fas and FGFR2 minigenes, promoting Fas exon 6 and FGFR2 exon K-SAM skipping, respectively. The repressor activity of hnRNP C1 on Fas exon 6 splicing is mediated by Hu antigen R (HuR). Experiments involving tethering approaches showed that the repressor capacity of hnRNP C1 is associated with an exonic splicing silencer in Fas exon 6. This effect was reversed by splice-site strengthening and is linked to its basic leucine zipper-like motif. These results suggest that hnRNP C1/C2 acts as a bridge between HuR and TIAR to modulate alternative Fas splicing.

EBV-positive diffuse large B-cell lymphoma of the elderly with dual genotype and aberrant TIA-1 expression: a case report and review of literature

B-cell lymphomas generally do not express T-cell intracellular antigen-1 (TIA-1), a cytotoxic granule-associated protein. We report a case of EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly with aberrant expression of TIA-1. The patient was an 84-year-old man with a history of progressively enlarged left parotid mass and mild facial paresis for 2 months. The incisional biopsy revealed sheets of medium to large lymphoma cells with focal angiocentricity and extensive tumor necrosis; only a few scattered small lymphocytes were noted among the lymphoma cells. Immunohistochemistry in formalin-fixed paraffin-embedded tissue demonstrated that the lymphoma cells marked with CD20, CD30, CD45 (focal), CD79a, BCL2 (focal and weak), PAX5, Oct2, BOB.1, IRF4/MUM1, EBV-LMP1, and TIA-1, but they did not mark with CD3, CD4, CD5, CD7, CD8, CD10, CD15, CD23, CD56, CD57, CD138, kappa and lambda immunoglobulin light chains, BCL6, βF1, granzyme B, or perforin. The aberrant TIA-1 expression was then confirmed by two different autostainers. EBV-encoded RNA (EBER) in situ hybridization was positive in the lymphoma cells. Gel electrophoresis for immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements revealed no definite clonal band, but fluorescence capillary electrophoresis demonstrated positive results for both IgH and TCR genes. Finally, we concluded this case as an EBV-positive DLBCL of the elderly with dual genotype (rearrangements of both IgH and TCR genes) and aberrant TIA-1 protein expression.

Fragile X‐related protein FXR1 controls post‐transcriptional suppression of lipopolysaccharide‐induced tumour necrosis factor‐α production by transforming growth factor‐β1

Tumour necrosis factor-alpha (TNF-alpha) is a key mediator of inflammation in host defence against infection and in autoimmune disease. Its production is controlled post-transcriptionally by multiple RNA-binding proteins that interact with the TNF-alpha AU-rich element and regulate its expression; one of these is Fragile X mental retardation-related protein 1 (FXR1). The anti-inflammatory cytokine transforming growth factor-beta1 (TGF-beta1), which is involved in the homeostatic regulation of TNF-alpha, causes post-transcriptional suppression of lipopolysaccharide (LPS)-induced TNF-alpha production. We report here that this depends on FXR1. Using RAW 264.7 cells and bone marrow-derived macrophages (BMDMphi) stimulated with LPS and TGF-beta1, we show that TGF-beta1 inhibits TNF-alpha protein secretion, whereas TNF-alpha mRNA expression remains unchanged. This response is recapitulated by the 3'-UTR of TNF-alpha, which is known to bind FXR1. TGF-beta1 induces FXR1 with a pattern of expression distinct from that of tristetraprolin, T-cell intracellular antigen 1, or human antigen R. When FXR1 is knocked down, TGF-beta1 is no longer able to inhibit LPS-induced TNF-alpha protein production, and overexpression of FXR1 suppresses LPS-induced TNF-alpha protein production. Targeting the p38 mitogen-activated protein kinase pathway of LPS-treated cells with small molecule inhibitors can induce FXR1 protein and mRNA expression. In summary, TGF-beta1 opposes LPS-induced stabilization of TNF-alpha mRNA and reduces the amount of TNF-alpha protein, through induction of expression of the mRNA-binding protein FXR1.

A case of CD4+/CD56+ hematodermic neoplasm (plasmacytoid dendritic cell neoplasm)

CD4+/CD56+ hematodermic neoplasm (blastic plasmacytoid dendritic cell neoplasm) involving the skin is relatively rare and has been of significant interest in the recent literature. We report here a 64-year-old male who presented with multiple purple-red nodules and plaques on his face, back, and chest. Histological examination of skin biopsies showed an intense hematolymphoid infiltration in the dermis and in the subcutaneous tissue. Stains were positive for CD4 (weak), CD56, and terminal deoxynucleotidyl transferase (TdT). These cells were negative for CD2, CD3, CD5, CD10, CD20, CD30, CD68, and T cell intracellular antigen (TIA). In situ hybridization (ISH) for Epstein-Barr virus was negative and the diagnosis was blastic NK cell lymphoma. The patient was treated with a hyper-CVAD regimen (cyclophosphamide, vincristine, doxorubicine, dexamethasone, methotrexate, and cytarabine).This treatment regimen achieved partial remission but the patient died eight months after the diagnosis. The patient presented with exclusively cutaneous involvement at the beginning but progressed rapidly and died shortly after despite aggressive chemotherapy. Due to its rarity, we present here a case of CD4+/CD56+ hematodermic neoplasm.

Extranodal Natural Killer Cell/T-Cell Lymphoma, Nasal Type, Presenting as Cutaneous Nodules and a Small-Bowel Perforation

Extranodal natural killer (NK) cell/T-cell lymphoma, nasal type, is a rare aggressive neoplasm, most commonly presenting as a destructive lesion in the nasal cavity and nasopharynx in middle-aged to older adults. About one third of cases present in an extranasal location, commonly involving skin and gastrointestinal tract, and usually occur in the absence of superficial lymphadenopathy. Diagnosis of this malignancy can be missed given its rarity and heterogeneous presentation. We describe a patient with an extranodal NK cell/T-cell lymphoma, nasal type, who was initially diagnosed and treated for a presumed Mycobacterium marinum infection, after biopsies were unrevealing. However, after more serious complications developed, repeat biopsy was performed. An atypical lymphocytic infiltrate was noted, with cells being positive for NK cell/T-cell markers CD2, CD7, and CD3 (subset), as well as for cytotoxic lymphocyte markers perforin, T-cell intracellular antigen, and CD56. In situ hybridization for Epstein-Barr virus-encoded RNA was also positive. This case demonstrates an important diagnostic pitfall of confusing cutaneous involvement by an aggressive NK cell/T-cell lymphoma with an antibiotic-resistant infection. Repeat biopsies and close clinicopathologic correlation are essential for establishment of correct diagnosis.

Changes in expression of sensory organ-specific microRNAs in rat dorsal root ganglia in association with mechanical hypersensitivity induced by spinal nerve ligation

Chronic neuropathic pain caused by peripheral nerve injury is associated with global changes in gene expression in damaged neurons. To understand the molecular mechanisms underlying neuropathic pain, it is essential to elucidate how nerve injury alters gene expression and how the change contributes to the development and maintenance of chronic pain. MicroRNAs are non-protein-coding RNA molecules that regulate gene expression in a wide variety of biological processes mainly at the level of translation. This study investigated the possible involvement of microRNAs in gene regulation relevant to neuropathic pain. The analyses focused on a sensory organ-specific cluster of microRNAs that includes miR-96, −182, and −183. Quantitative real-time polymerase chain reaction (qPCR) analyses confirmed that these microRNAs were highly enriched in the dorsal root ganglion (DRG) of adult rats. Using the L5 spinal nerve ligation (SNL) model of chronic neuropathic pain, we observed a significant reduction in expression of these microRNAs in injured DRG neurons compared to controls. In situ hybridization and immunohistochemical analyses revealed that these microRNAs are expressed in both myelinated (N52 positive) and unmyelinated (IB4 positive) primary afferent neurons. They also revealed that the intracellular distributions of the microRNAs in DRG neurons were dramatically altered in animals with mechanical hypersensitivity. Whereas microRNAs were uniformly distributed within the DRG soma of non-allodynic animals, they were preferentially localized to the periphery of neurons in allodynic animals. The redistribution of microRNAs was associated with changes in the distribution of the stress granule (SG) protein, T-cell intracellular antigen 1 (TIA-1). These data demonstrate that SNL induces changes in expression levels and patterns of miR-96, −182, and −183, implying their possible contribution to chronic neuropathic pain through translational regulation of pain-relevant genes. Moreover, SGs were suggested to be assembled and associated with microRNAs after SNL, which may play a role in modification of microRNA-mediated gene regulation in DRG neurons.

Sam68 relocalization into stress granules in response to oxidative stress through complexing with TIA-1

Sam68 has been implicated in a variety of important cellular processes such as RNA metabolism and intracellular signaling. We have recently shown that Sam68 cytoplasmic mutants induce stress granules (SG) and inhibit HIV-1 nef mRNA translation [J. Henao-Mejia, Y. Liu, I.W. Park, J. Zhang, J. Sanford, J.J. He, Suppression of HIV-1 Nef translation by Sam68 mutant-induced stress granules and nef mRNA sequestration, Mol. Cell 33 (2009) 87–96]. These findings prompted us to investigate the possibility and the underlying mechanisms of the wild-type counterpart Sam68 SG recruitment. Herein, we revealed that Sam68 was significantly recruited into cytoplasmic SG under oxidative stress. We then demonstrated that domain aa269–321 and KH domain were both essential for this recruitment. Nevertheless, Sam68 knockdown had no effects on SG assembly, indicating that Sam68 is not a constitutive component of the SG. Moreover, we showed that Sam68 cytoplasmic mutant-induced SG formation was independent of eIF2α phosphorylation. Lastly, we demonstrated that Sam68 was complexed with T-cell intracellular antigen-1 (TIA-1), a core SG component, and that the complex formation was correlated with Sam68 SG recruitment. Taken together, these results provide direct evidence for the first time that Sam68 is recruited into SG through complexing with TIA-1 in response to oxidative stress and suggest that cytoplasmic SG recruitment of Sam68 and ensuing changes in Sam68 physiological functions are part of the host response to external stressful conditions.

Nasal-type extranodal natural killer/T-cell lymphoma presenting with extensive leg ulcers

Primary cutaneous T-cell lymphomas are rare and can be difficult to classify precisely. We present a case of extranodal natural killer (NK)/T-cell lymphoma in a previously healthy, immunocompetent man who presented with extensive necrotic leg ulcers and disseminated skin nodules. Immunohistochemical studies revealed that the tumour cells were positive for CD3, CD30, granzyme B and T-cell intracellular antigen-1, and negative for CD5 and CD56, with positive staining for Epstein-Barr virus (EBV) RNA on in situ hybridization. A diagnosis of extranodal NK/T-cell lymphoma was made, based on the presence of cytotoxic granules and positive EBV RNA staining. The patient was treated with a regimen of chemotherapy comprising corticosteroids, intravenous methotrexate, ifosphamide, L-asparaginase and etoposide with initial response.

Acute Presentation of Nasal-Type Natural Killer/T-cell Lymphoma of the Orbit

An unusual case of nasal-type natural killer/T-cell lymphoma (NKTL) of the orbit is reported. The clinical history, computed tomography, magnetic resonance imaging, and biopsy specimen of a 29-year-old man with a right orbital lymphoma were evaluated. The patient initially presented with conjunctival injection and had flu-like symptoms before developing right proptosis and reduced vision; imaging showed a diffuse infiltrative process throughout the orbit. Orbital biopsy revealed angiodestruction with prominent necrosis, and angiocentric lymphoma growth and lymphoma cells were positively stained for CD3, CD20, CD45RO, CD56, cytotoxic molecules (granzyme B and T-cell intracellular antigen-1), and Epstein-Barr virus. NKTL is rare and may present acutely; the imaging findings presented serve to highlight the radiologic features of the disease.

Inhibition of G1 to S Phase Progression by a Novel Zinc Finger Protein P58TFL at P-bodies

We recently reported the translocation of the immunoglobulin (Ig) light chain kappa locus gene with a possible tumor suppressor gene, TFL, in transformed follicular lymphoma. However, the functional significance in cell transformation remains to be elucidated. Here, we first identified two gene products, P58(TFL) and P36(TFL), derived by alternative splicing. The expression was prominent in normal human lymphocytes but defective in some leukemia/lymphoma cell lines. Overexpression of either protein in a mouse pro-B cell line, Ba/F3, and a human leukemia cell line, Jurkat, inhibited G(1) to S phase progression through suppression of retinoblastoma protein (Rb) phosphorylation. The dominant gene product, P58(TFL), colocalized with mRNA-processing body markers, eukaryotic translation initiation factor 2C and DCP1 decapping-enzyme homolog A, but not with a stress granule maker, T-cell intracellular antigen 1, in the cytoplasm. Taken together with the unique CCCH-type zinc finger motif, the present study suggests that P58(TFL) could play an important role in the regulation of cell growth through posttranscriptional modification of cell cycle regulators, at least partially, upstream of Rb.

Epstein-Barr virus-associated proliferative disorder presenting as Hodgkin's lymphoma and developing as aggressive natural killer-cell leukemia 19 years later: A case report of composite lymphoma

We describe a patient who was diagnosed as having classic Hodgkin's lymphoma at 29 years of age, and aggressive natural killer-cell leukemia at 48 years. He died 42 days later. Hodgkin and Reed–Sternberg cells in the lymph node expressed CD30, CD15, T-cell intracellular antigen-1 (TIA-1), perforin, granzyme B, and Epstein-Barr virus-encoded RNA (EBER). Natural killer-cell leukemia cells in the bone marrow expressed cytoplasmic CD3ε, TIA-1, perforin, granzyme B, and EBER, and some neoplastic cells expressed CD56 (123C3). Fluorescence-activated cell sorter (FACS) analysis showed that neoplastic cells expressed CD56. Neither a rearrangement band of the T-cell receptor gene nor that of the immunoglobulin heavy chain gene was detected. Chromosomal abnormalities were noted.

CD4+, CD56+ Mycosis Fungoides: Case Report and Review of the Literature

This case report details an 85-year-old woman who presented with mycosis fungoides (MF), clinical stage 1A. Bilateral lesions on the upper thighs were responsive to topical steroid therapy. Biopsies showed band-like dermal infiltrates of medium-sized lymphocytes with marked epidermotropism, including large intraepidermal lymphocytes with nuclear convolutions, consistent with MF. Immunohistochemical staining revealed that the lesional cells were CD56+, but unlike the case in previous reports of CD56+ MF, they also expressed CD4 and T-cell intracellular antigen 1 and did not express CD8. To our knowledge, this is the first description of a case of MF with a CD4+, CD8-, CD56+, T-cell intracellular antigen 1-positive immunophenotype. At 85 years of age, the patient is older than all previously described patients with CD56+ MF. Despite an immunophenotype observed more commonly in aggressive forms of cutaneous T-cell lymphoma, the clinical presentation is that of typical MF. The patient presented with limited disease and after 12 months of follow-up has not progressed beyond stage 1A.

Depletion of T-cell intracellular antigen proteins promotes cell proliferation

The transcriptome of TIA-1/TIAR-depleted cells indicates roles in inflammation, cell-cell signaling, immune suppression, angiogenesis, metabolism and cell proliferation.

Primary Intestinal Intraepithelial Natural Killer–like T-Cell Lymphoma: Case Report of a Distinct Clinicopathologic Entity

Intestinal T-cell lymphoma is a heterogenous group. These tumors differ in their association with enteropathy, intraepithelial or nonintraepithelial origin, primary or secondary involvement, and T-cell or natural killer-like T-cell immunophenotype. There are also nonneoplastic conditions, such as celiac disease, refractory sprue, and reactive T-cell infiltration that mimic intestinal T-cell lymphoma. Therefore, the differential diagnosis requires extensive morphologic, immunophenotypic, and molecular genetic studies. A subset of primary intestinal intraepithelial T-cell lymphoma has emerged in recent years that is distinguished from enteropathy-type T-cell lymphoma in terms of clinical presentation (nonenteropathic), morphology (monomorphic small to medium-sized cells), immunophenotype (CD3(-)CD8(+)CD56(+)), and cytogenetics. We report such a case with a unique immunophenotype (CD3(-), cytoplasmic CD3(+), CD4(-), CD8(+), CD5(-), CD7(+), CD16(-), CD56(+), CD57(-), CD103(+), T-cell intracellular antigen 1(+), and betaF1(+)) that is comparable to that of a newly identified subset of intraepithelial T cells. The tumor progressed rapidly and the patient died within 6 months after the onset of the disease. We recommend a large monoclonal antibody panel for the differential diagnosis of this heterogeneous group of T-cell lymphoma.

Primary intestinal intraepithelial natural killer-like T-cell lymphoma: case report of a distinct clinicopathologic entity.

Abstract Intestinal T-cell lymphoma is a heterogenous group. These tumors differ in their association with enteropathy, intraepithelial or nonintraepithelial origin, primary or secondary involvement, and T-cell or natural killer–like T-cell immunophenotype. There are also nonneoplastic conditions, such as celiac disease, refractory sprue, and reactive T-cell infiltration that mimic intestinal T-cell lymphoma. Therefore, the differential diagnosis requires extensive morphologic, immunophenotypic, and molecular genetic studies. A subset of primary intestinal intraepithelial T-cell lymphoma has emerged in recent years that is distinguished from enteropathy-type T-cell lymphoma in terms of clinical presentation (nonenteropathic), morphology (monomorphic small to medium-sized cells), immunophenotype (CD3−CD8+CD56+), and cytogenetics. We report such a case with a unique immunophenotype (CD3−, cytoplasmic CD3+, CD4−, CD8+, CD5−, CD7+, CD16−, CD56+, CD57−, CD103+, T-cell intracellular antigen 1+, and βF1+) that i...