Tissue-resident memory T cells (TRM) contained at sites of previous infection provide local protection against reinfection. Whether they form and function in organ transplants where cognate antigen persists is unclear. This is a key question in transplantation as T cells are detected long term in allografts, but it is not known whether they are exhausted or are functional memory T cells. Using a mouse model of kidney transplantation, we showed that antigen-specific and polyclonal effector T cells differentiated in the graft into TRM and subsequently caused allograft rejection. TRM identity was established by surface phenotype, transcriptional profile, and inability to recirculate in parabiosis and retransplantation experiments. Graft TRM proliferated locally, produced interferon-γ upon restimulation, and their in vivo depletion attenuated rejection. The vast majority of antigen-specific and polyclonal TRM lacked phenotypic and transcriptional exhaustion markers. Single-cell analysis of graft T cells early and late after transplantation identified a transcriptional program associated with transition to the tissue-resident state that could serve as a platform for the discovery of therapeutic targets. Thus, recipient effector T cells differentiate into functional graft TRM that maintain rejection locally. Targeting these TRM could improve renal transplant outcomes.
Idiopathic granulomatous mastitis is a rare benign inflammatory breast disease that affects women of childbearing age with a history of breastfeeding. It usually presents as an enlarging breast mass that can greatly mimic breast cancer. Moreover, it does not have a specific radiographic finding, so the only way to reach a definitive diagnosis is by core biopsy and histology. Furthermore, a consensus regarding the best treatment modality has not been reached yet. In this report, we describe the cases of two patients who suffered from this disease, and to our knowledge, such a report is the first of its kind to address this topic in this region. Therefore, because of its uncommon nature and obscure presentation, we hereby report two cases of idiopathic granulomatous mastitis. The clinical presentation, treatment, and pathological findings are described, and a literature review on idiopathic granulomatous mastitis will be reported.
Objectives
SOX10 expression helps identify melanocytic lesions. Over time, novel uses have been identified, such as expression in triple-negative breast cancer (TNBC). We evaluated the usefulness of SOX10 in breast pathology—specifically, identification and subtyping of TNBC and distinction from gynecologic carcinomas, use as a myoepithelial marker, and in the distinction of usual ductal hyperplasia (UDH) from atypical ductal hyperplasia (ADH).
Methods
Several breast and gynecologic carcinoma tissue microarrays containing a total of 492 cases were stained with SOX10. Whole sections of 34 ADH, 50 UDH, and 29 ductal carcinoma in situ (DCIS) samples were also stained with SOX10.
Results
SOX10 expression was identified in 67% of consecutive TNBC cases. Expression was mostly seen in nonapocrine, androgen receptor (AR)–negative TNBCs. All gynecologic carcinomas (n = 157) were negative. All UDH cases showed mosaic SOX10 expression, while all ADH cases lacked expression. All estrogen receptor (ER)–positive DCIS (n = 19) specimens were negative for SOX10, while 2 of 10 ER-negative DCIS specimens were positive for SOX10. The latter 2 cases showed SOX10-positive invasive carcinomas.
Conclusions
SOX10 identifies nonluminal AR-type TNBC and is useful in distinguishing TNBC from gynecologic carcinomas. SOX10 can distinguish UDH from ADH. SOX10 is not useful in distinguishing ADH from DCIS.
The role of TRM in transplantation is unknown. In this study, we investigated the formation and function of TRM in a mouse kidney transplantation model.
(B6xBALB/c) F1.ova kidneys were transplanted to B6 recipients and 1m OT-I Teff cells transferred on day 2. Graft, blood, bone marrow, SLO, and liver were harvested 4 and 8 wks after transplantation. TRM were identified as CD44hiCD62LlowCD69+ CD103+/− cells after excluding in vivo labeled T cells. OT-I and polyclonal TRM were transcriptionally characterized using scRNAseq. TRM residency was tested by parabiosis and re-transplantation. To further establish a causal relationship between the TRM OT-Is and rejection we depleted them at wk 4 post adoptive transfer using anti-Thy1.1 (250 ug IV per day for 7d).
Mean serum creatinine (mg/dl) was significantly higher in allo vs syn group at wk 8 (0.7 vs 0.2, p<0.05). Graft histology showed mixed acute and chronic rejection in the allo group. Flow analysis of allograft cells demonstrated TRM cells among OT-I and endogenous T cell populations at 4 & 8 wks. The OT-I population was exclusively TRM phenotype by flow and scRNAseq, rapidly produced IFNγ upon re-stimulation, and was not detected anywhere else. There was no significant difference in mean number of OT-Is between wk 4 and wk 8 (277K vs 234k, p=0.74). OT-I T cells could not be detected in the parabiont kidney graft or tissues or in the secondary host outside the re-transplanted kidney, indicating that the TRM are indeed resident in the graft and do not re-circulate. Depleting the OT-Is preserved kidney function at wk 8 compared to the non-depleted group (Cr= 0.7 vs 0.2, p<0.05).
Our findings show that donor-specific TRM form in kidney allografts, are functional, and contribute to rejection.
Breast cancer rarely metastasizes to the uterus. In particular, lobular carcinoma of the breast more commonly spreads to the uterus when compared to invasive ductal carcinoma. PET-CT can be a tool to differentiate between fibroids and metastasis based on the maximum standardized uptake value (SUVmax). The authors report the case of a 37-year-old female with invasive ductal carcinoma (IDC) having significantly fluorodeoxyglucose (FDG)-avid masses on PET-CT which were later found to be metastases.
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