Tumor Immune Evasion Induced by Dysregulation of Erythroid Progenitor Cells Development

Abstract

Cancer cells harness normal cells to facilitate tumor growth and metastasis. Within this complex network of interactions, the establishment and maintenance of immune evasion mechanisms are crucial for cancer progression. The escape from the immune surveillance results from multiple independent mechanisms. Recent studies revealed that besides well-described myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) or regulatory T-cells (Tregs), erythroid progenitor cells (EPCs) play an important role in the regulation of immune response and tumor progression. EPCs are immature erythroid cells that differentiate into oxygen-transporting red blood cells. They expand in the extramedullary sites, including the spleen, as well as infiltrate tumors. EPCs in cancer produce reactive oxygen species (ROS), transforming growth factor β (TGF-β), interleukin-10 (IL-10) and express programmed death-ligand 1 (PD-L1) and potently suppress T-cells. Thus, EPCs regulate antitumor, antiviral, and antimicrobial immunity, leading to immune suppression. Moreover, EPCs promote tumor growth by the secretion of growth factors, including artemin. The expansion of EPCs in cancer is an effect of the dysregulation of erythropoiesis, leading to the differentiation arrest and enrichment of early-stage EPCs. Therefore, anemia treatment, targeting ineffective erythropoiesis, and the promotion of EPC differentiation are promising strategies to reduce cancer-induced immunosuppression and the tumor-promoting effects of EPCs.

Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy

“…As known, hemoglobin levels have a prognostic role in cancers ( 41 ) and are predictive for response to various anti-cancer therapies, especially when combined with albumin, lymphocyte, and platelet levels ( 42 ). It has been also reported that, regardless of its causes, hemoglobin levels could influence the activation status of T cells against cancer ( 43 , 44 ). Other authors also reported an association between higher hemoglobin levels and better clinical outcomes both in CSCC and lung cancer patients treated with PD-1 inhibitor ( 24 , 45 ).…”

Ultrasound-Targeted Microbubble Destruction Alleviates Immunosuppression Induced by CD71+ Erythroid Progenitor Cells and Promotes PDL-1 Blockade Immunotherapy in the Lewis Lung Cancer Model

“…The systemic immunity in cancer beyond the TME is essential for effective immune response toward immunotherapy, and the tumor immune macroenvironment is remarkably plastic (2)(3)(4). Recently, immature red blood cells called CD71 + erythroid progenitor cells (CECs) or erythroid progenitor cells (EPCs) were identified as regulators of the immune response in cancer (5,6). The CD71/Ter119 combination-marked CECs reflect the dynamic maturation of red blood cells, which define the nucleated erythrocytes (7).…”

Potent but transient immunosuppression of T-cells is a general feature of CD71+ erythroid cells

“…Moreover, CECs at the earliest stages of differentiation are relatively rare in healthy individuals 45 . Thus, it seems that CECs may have the most significant immunoregulatory role under conditions that are characterized by the impaired erythroid differentiation and robust enrichment of early-stage CECs, that include cancer 55 .…”