T-cell dysfunctions in myelodysplastic syndromes

Abstract

Escape from immune surveillance is a hallmark of cancer. Immune deregulation caused by intrinsic and extrinsic cellular factors, such as altered T cell functions, leads to immune exhaustion, loss of immune surveillance, and clonal proliferation of tumoral cells. The T cell immune system contributes to the pathogenesis, maintenance, and progression of myelodysplastic syndrome (MDS). Here, we comprehensively reviewed our current biological knowledge of the T cell compartment in MDS and recent advances in the development of immunotherapeutic strategies, such as immune checkpoint inhibitors and T cell- and antibody-based adoptive therapies, that hold promise to improve the outcome of MDS patients.

Single-cell analysis of bone marrow CD8+ T cells in Myeloid Neoplasms predicts response to treatment with Azacitidine

“…25 In AML and MDS, several CD8 + T cell defects have been described that are potentially reversible by various treatments, including AZA. 9,11,36 However, the architecture of CD8 + T cell immunity and its impact on the clinical behavior of AML and MDS are still incompletely understood, thus hampering the development of successful immunotherapeutic approaches.…”

“…[5][6][7] In particular, CD8 + T cells play a crucial role in the regulation of tumor microenvironment. 8 Aberrant functionality of CD8 + T cells has been observed in patients with myeloid neoplasms compared to healthy individuals, [9][10][11] rendering the former cell subset a major target for immunotherapeutic interventions. 12,13 The standard of care for patients with higher-risk MDS (HR-MDS) and non-proliferating CMML, as well as patients with secondary AML, who are not eligible for intensive chemotherapy, is treatment with hypomethylating agents (HMA) like azacitidine (AZA).…”

“…5–7 In particular, CD8 + T cells play a crucial role in the regulation of tumor microenvironment. 8 Aberrant functionality of CD8 + T cells has been observed in patients with myeloid neoplasms compared to healthy individuals, 9–11 rendering the former cell subset a major target for immunotherapeutic interventions. 12,13…”