Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Abstract
Regulatory T cells play an important role in the maintenance of immunological self-tolerance by suppressing immune responses against autoimmune diseases and cancer. Little is known, however, about the nature of the physiological target antigens for CD4+ regulatory T (Treg) cells. Here we report the identification of the LAGE1 protein as a ligand for tumor-specific CD4+ Treg cell clones generated from the tumor-infiltrating lymphocytes (TILs) of cancer patients. Phenotypic and functional analyses demonstrated that they were antigen-specific CD4+ Treg cells expressing CD25 and GITR molecules and possessing suppressive activity on the proliferative response of naive CD4+ T cells to anti-CD3 antibody stimulation. Ligand-specific activation and cell-cell contact were required for TIL102 Treg cells to exert suppressive activity on CD4+ effector cells.

• These findings suggest that the presence of tumor-specific CD4+ Treg cells at tumor sites may have a profound effect on the inhibition of T cell responses against cancer.

https://www.sciencedirect.com/science/a ... 1303003595

A great pdf comparison of PD1 verses PDL1 .

https://pdfs.semanticscholar.org/fd8d/f ... 5d19fc.pdf

Ligand 1 paper , on ASPS




Alveolar soft part sarcoma (ASPS) has often proven to be resistant to conventional doxorubicin-based chemotherapy, but tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) may provide new treatment strategies for this rare type of sarcoma, according to a literature review.

A rare, translocation-driven sarcoma of the soft tissues, ASPS often affects young adults and is characterized by indolent behavior and early metastasis. Despite its resistance to chemotherapy, studies indicate that survival is often prolonged in patients with metastatic disease. The literature has shown 5-year survival rates at about 60%, and this percentage has remained fairly consistent for the past 3 decades.

Luca Paoluzzi, MD, of New York University, and Robert G. Maki, MD, PhD, of Hofstra University, Hempstead, N.Y., reviewed the literature from 1952 to March 2018, in order to gain a better understanding of ASPS and the opportunities “for the translation of such knowledge into clinical practice,” they wrote in JAMA.

From a therapeutic standpoint, ASPS is characterized by sensitivity to vascular endothelial growth factor receptor–predominant TKIs, compared with other soft tissue sarcomas (STS), and recent data have emphasized that it is responsive to new immunotherapy regimens including ICIs. Pazopanib is currently the only agent that has received regulatory approval for use in STS refractory to other treatments and it appears to have consistent activity in metastatic ASPS. Management of ASPS generally also involves surgical resection and/or systemic treatment for metastatic disease. Conventional agents such as anthracycline-based chemotherapy have demonstrated a poor response rate lower than 10%, and while a complete resection may be curative, metastases are common and can occur years after resection of the primary tumor.

Conversely, ICIs “represent a promising area of drug development in ASPS; the data to date are limited but encouraging,” wrote Dr. Paoluzzi and Dr. Maki.

They pointed to one study that included 50 patients with sarcoma with 14 different subtypes of STS who were enrolled in immunotherapy trials conducted at the University of Texas MD Anderson Cancer Center, Houston. There were two pretreated patients with ASPS (two to four prior lines) in the cohort who received antiprogrammed death-ligand 1–based therapy, and achieved a partial response bordering on a complete response that lasted 8 and 12 months. An additional two patients achieved stable disease.

Another paper, presented at the 2017 Connective Tissue Oncology Society annual meeting, presented preliminary data from a phase 2 study that showed four of nine evaluable patients with ASPS treated with the TKI axitinib, combined with pembrolizumab, achieved a partial response. Three others had stable disease.

“Pathway-driven basket trials facilitate the enrollment of patients with such uncommon cancers and should provide valuable information regarding a second type of immune responsiveness to ICIs, one that is not a function of high tumor mutational burden,” the authors concluded.

No outside funding sources were reported. Dr. Maki reported receiving consultant fees from numerous sources and research support to New York University from Immune Design, Immunocore, Eli Lilly, Presage Biosciences, TRACON Pharmaceuticals, SARC, Regeneron, and Genentech. No other conflicts were reported.

SOURCE: Paoluzzi L et al. JAMA Oncol. 2018 Oct 18. doi: 10.1001/jamaoncol.2018.4490.




https://www.mdedge.com/sarcomajournal/a ... -soft-part

Olga
Delete if need be but cytomegalovirus is quite the link, in my opinion .


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