Inhibition of Phagocytosis and Glucose Metabolism of Alveolar Macrophages during Pulmonary Tumour Growth

Gudewicz, Paul W.; Saba, Thomas M.

doi:10.1038/bjc.1977.249

Cited by 10 publications

(3 citation statements)

References 23 publications

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“…RpS6 P−/− mice also have reduced glucose disposal capacity due to a 2-fold reduction in secretion of circulating and pancreatic insulin by small β-cells (Ruvinsky et al, 2005). In at least one study, intravenous injection of mice with rat breast carcinoma cells results in poorly phagocytic alveolar macrophages with reduced cell-autonomous glucose oxidation that leads to tumor metastasis (Gudewicz and Saba, 1977). It will be interesting to ask whether reduced glucose oxidation in these alveolar macrophages correlates with reduced glucose homeostasis due to defective RpS6 regulation.…”

Section: Discussionmentioning

confidence: 99%

The Pallbearer E3 Ligase Promotes Actin Remodeling via RAC in Efferocytosis by Degrading the Ribosomal Protein S6

et al. 2015

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Clearance of apoptotic cells (efferocytosis) is achieved through phagocytosis by professional or amateur phagocytes. It is critical for tissue homeostasis and remodeling in all animals. Failure in this process can contribute to the development of inflammatory autoimmune or neurodegenerative diseases. We previously found that the PALL-SCF E3-Ubiquitin ligase complex promotes apoptotic cell clearance, yet it remained unclear as to how it did so. Here, we show that the F-Box protein PALL interacts with phosphorylated Ribosomal protein S6 (RpS6) to promote its ubiquitylation and proteasomal degradation. This leads to RAC2 GTPase up-regulation and activation and F-actin remodeling that promotes efferocytosis. We further show that the specific role of PALL in efferocytosis is driven by its apoptotic cell-induced nuclear export. Finding a role for RpS6 in negatively regulating efferocytosis provides the opportunity to develop new strategies to regulate this process.

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Section: Discussionmentioning

confidence: 99%

The Pallbearer E3 Ligase Promotes Actin Remodeling via RAC in Efferocytosis by Degrading the Ribosomal Protein S6

et al. 2015

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“…The importance of having a thorough understanding of tumor-associated macrophages (TAM), for example, is underscored by clinical data that reveal TAM correlate with poor prognosis and negatively impact efficacy of checkpoint-inhibitor therapy in patients with cancer [1][2][3][4][5][6][7][8]. However, although it has been over 40 years since altered metabolism and effector function of TAM were reported [9], exactly when and how pro-tumor TAM arise has yet to be well defined. The current paradigm is that tumor progression over time creates an environment that leads to the generation of pro-tumor TAM which then further potentiates tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Indicators of a pro-tumor immune response are evident at early stages of breast cancer

Zhang

Kurt

2020

Clin Transl Oncol

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With advances in checkpoint inhibitor and CAR T-cell therapies, among other advances in immunotherapy, this is an exciting time to be a tumor immunologist. We are witnessing the transition of decades of work at the bench leading to substantial success in the clinic. While work continues developing new and improving existing immunotherapies, there remains a great deal of basic tumor immunology still to learn, information that can only lead to greater success in the clinic. One area in need of more attention is understanding the immune response at early stages of breast cancer. While there is no question that early diagnosis and treatment save lives, a greater understanding about the immune response during early stages of breast cancer may reveal information that could assist in monitoring individuals at risk of breast cancer, and could have implications for patients diagnosed at early stages of disease, and may provide important information about the origins of an immune-suppressive environment. Here, we review studies that have looked at the very early immune response to breast cancer focusing on patients with DCIS, before invasion in spontaneous transgenic murine mammary carcinoma models, and before transplantable or orthotopic murine mammary carcinoma models become palpable. The findings revealed that indicators of a pro-tumor immune response are already present at early stages of disease.

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“…In contrast, macrophages of animals bearing growing tumours are shown to express tumoricidal activity in response to appropriate activation stimuli (Meltzer & Stevenson, 1978; Sone & Fidler, 1981). Similarly, some (Meltzer & Stevenson, 1977;Sone & Fidler, 1981) but not all (Gudewicz & Saba, 1977) reports have shown that the phagocytic abilities of macrophages remain intact even in the presence of tumours. Most of these findings regarding antitumour functions of macrophages come from murine studies.…”

mentioning

confidence: 98%

Antitumour potential of pleural cavity macrophages in lung cancer patients without malignant effusion

Kimura

Sone²,

Takahashi³

et al. 1989

Br J Cancer

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Summary The present study was undertaken to examine whether the presence of primary lung cancer could affect the antitumour activities of pleural cavity macrophages (PCM) and peripheral blood monocytes (PBM). PCM by pleural lavage and PBM were simultaneously obtained from 14 lung cancer patients not showing invasion of the pleural cavity. PCM and PBM were isolated by percoll gradient centrifugation and adherence. The lavage method yielded about 16.8 +9.6 (s.e.) x 106 cells, which consisted of 80.7% PCM, 17.6% lymphocytes and 1.6% other cells. The cytotoxic activities of PCM and PBM against allogeneic melanoma (A375) cells were assessed by a 72 h 125I-IUdR release assay. The lavaged PCM showed spontaneously high tumour cytotoxic activity which was dependent on the effector/target ratio. In 13 out of 14 cancer patients, PCM were significantly more cytotoxic to melanoma cells than PBM. In contrast, there were no significant differences in production of tumour necrosis factor (TNF-a) or interleukin (IL-l) between PCM and PBM. When the abilities of PCM and PBM of the same patient to produce these monokines were compared, PCM produced much more TNF-cx than PBM, thus indicating a correlation between the expression of spontaneous macrophage-mediated cytotoxicity and spontaneous TNF-a production by PCM. These results suggest that PCM may play an important role in host defence against invasion of the pleural cavity by cancer cells.

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Inhibition of Phagocytosis and Glucose Metabolism of Alveolar Macrophages during Pulmonary Tumour Growth

Cited by 10 publications

References 23 publications

The Pallbearer E3 Ligase Promotes Actin Remodeling via RAC in Efferocytosis by Degrading the Ribosomal Protein S6

The Pallbearer E3 Ligase Promotes Actin Remodeling via RAC in Efferocytosis by Degrading the Ribosomal Protein S6

Indicators of a pro-tumor immune response are evident at early stages of breast cancer

Antitumour potential of pleural cavity macrophages in lung cancer patients without malignant effusion

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