Exogenous remodeling of lung resident macrophages protects against infectious consequences of bone marrow-suppressive chemotherapy

Abstract

Infection is the single greatest threat to survival during cancer chemotherapy because of depletion of bone marrow-derived immune cells. Phagocytes, especially neutrophils, are key effectors in immunity to extracellular pathogens, which has limited the development of new approaches to protect patients with cancer and chemotherapy-induced neutropenia. Using a model of vaccineinduced protection against lethal Pseudomonas aeruginosa pneumonia in the setting of chemotherapy-induced neutropenia, we found a population of resident lung macrophages in the immunized lung that mediated protection in the absence of neutrophils, bone marrowderived monocytes, or antibodies. These vaccine-induced macrophages (ViMs) expanded after immunization, locally proliferated, and were closely related to alveolar macrophages (AMs) by surface phenotype and gene expression profiles. By contrast to AMs, numbers of ViMs were stable through chemotherapy, showed enhanced phagocytic activity, and prolonged survival of neutropenic mice from lethal P. aeruginosa pneumonia upon intratracheal adoptive transfer. Thus, induction of ViMs by tissue macrophage remodeling may become a framework for new strategies to activate immune-mediated reserves against infection in immunocompromised hosts.chemotherapy | neutropenia | vaccine | macrophage | Pseudomonas aeruginosa pneumonia

Bioreactor-based mass production of human iPSC-derived macrophages enables immunotherapies against bacterial airway infections

“…Given the impressive in vivo functionality of iPSC-Mac in the acute infection model, a potentially important extension of this work would be to evaluate the therapeutic efficacy of a macrophage-based immunotherapy in chronic infections with P. aeruginosa , as frequently observed in patients suffering from chronic obstructive pulmonary disease (COPD) 33 or cystic fibrosis (CF) 34 . As previously shown for endogenous alveolar macrophages 35 , iPSC-Mac might be induced towards a vaccine-induced macrophage (ViM) phenotype, which upon intra-pulmonary administration could protect mice from P. aeruginosa infections. This might be of particular interest in life-threatening, chemotherapy associated infections.…”

Role of the initial degree of anaemia and treatment model in the prognosis of gastric cancer patients treated by chemotherapy: a retrospective analysis

“…There were 312 patients treated with the first line chemotherapy regimens, yet the GC in 188 patients remained in a development condition, and then those patients were treated with the second or/and third line chemotherapy regimens including FOLFIRI and docetaxel single agent. The cycles of chemotherapy used for our GC patients was 4.4±3.705 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). 286 patients (47.8%) failed to receive further chemotherapy after 1-2 cycles of chemotherapy treatment.…”

Role of the initial degree of anaemia and treatment model in the prognosis of gastric cancer patients treated by chemotherapy: a retrospective analysis

“…There were 312 patients treated with the first line chemotherapy regimens, yet the GC in 188 patients remained in a development condition, and then those patients were treated with the second or/and third line chemotherapy regimens including FOLFIRI and docetaxel single agent. The cycles of chemotherapy used for our GC patients was 4.4±3.705 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). 286 patients (47.8%) failed to receive further chemotherapy after 1-2 cycles of chemotherapy treatment.…”

“…Cancer-related anaemia (CRA) is considered to be associated with multiple pathological and clinical factors, such as bleeding, nutritional deficiency, and bone marrow suppression (6). Bone marrow suppression can be caused by both malignant cell infiltration and chemotherapy treatment (7,8).…”