Major Histocompatibility Complex Class I–restricted Cross-presentation Is Biased towards High Dose Antigens and Those Released during Cellular Destruction

Naive T cells recirculate mainly within the secondary lymphoid compartment, but once activated they can enter peripheral tissues and perform effector functions. To activate naive T cells, foreign antigens must traffic from the site of infection to the draining lymph nodes, where they can be presented by professional antigen presenting cells. For major histocompatibility complex class I–restricted presentation to CD8+ T cells, this can occur via the cross-presentation pathway. Here, we investigated the conditions allowing antigen access to this pathway. We show that the level of antigen expressed by peripheral tissues must be relatively high to facilitate cross-presentation to naive CD8+ T cells. Below this level, peripheral antigens did not stimulate by cross-presentation and were ignored by naive CD8+ T cells, although they could sensitize tissue cells for destruction by activated cytotoxic T lymphocytes (CTLs). Interestingly, CTL-mediated tissue destruction facilitated cross-presentation of low dose antigens for activation of naive CD8+ T cells. This represents the first in vivo evidence that cellular destruction can enhance access of exogenous antigens to the cross-presentation pathway. These data indicate that the cross-presentation pathway focuses on high dose antigens and those released during tissue destruction

Fibroblast-Activated Protein Inhibitor PET/CT: Cancer Diagnosis and Management.

Fibroblast activation protein (FAP), overexpressed on cancer-associated fibroblasts (CAFs), is a novel target for molecular imaging of various tumors. Recently, the development of several small-molecule FAP inhibitors for radiolabeling with (68)Ga has resulted in the emergence of studies evaluating its clinical role in cancer imaging. Preliminary findings have demonstrated that, in contrast to radiotracers taking advantage of cancer-specific targets such as PSMA and DOTATATE, FAPs as a target are the most promising that can compete with (18)FDG in terms of widespread indications. They also have the potential to overcome the shortcomings of (18)FDG, particularly false-positive uptake due to inflammatory or infectious processes, low sensitivity in certain cancer types, and radiotherapy planning. In addition, the attractive theranostic properties may facilitate the treatment of many refractory cancers. This review summarizes the current FAP variants and related clinical studies, focusing on radiopharmacy, dosimetry, and diagnostic and theranostic applications

Ga-68-PSMA PET/CT and PET/MRI in high-risk prostate cancer patients

Treatment of high-risk prostate cancer (HRPCa) is challenging. Local staging and metastatic evaluation are important for the patient management. Recently, prostate-specific membrane antigen (PSMA)-based imaging modalities such as PSMA PET/CT and PET/MRI have received significant attention for detection of recurrent prostate cancer sites with elevated prostate-specific antigen levels, after therapy. Current evidence suggests that these imaging modalities may also have a role for the management of patients with HRPCa. In this review, we discuss PSMA-based imaging modalities in the management of patients with HRPCa