Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes

Allison, Katrina E.; Coomber, Brenda L.; Bridle, Byram W.

doi:10.1111/imm.12777

Cited by 88 publications

(81 citation statements)

References 105 publications

(304 reference statements)

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“…Pro‐metastatic effects of platelets are attributed to the adhesion of platelets to tumor cells, thereby providing a shield protecting against cell death, but also to platelet‐derived factors that enable cells to migrate from the bloodstream into visceral organs . Lymphocytes, on the other hand, are thought to have an antitumor effect through their ability to specifically target and then kill cancer cells . From this, it would logically follow that individuals with increased levels of neutrophils and platelets and/or decreased levels of lymphocytes are at a higher risk of developing cancer.…”

Section: Discussionmentioning

confidence: 99%

“…31,32 Lymphocytes, on the other hand, are thought to have an antitumor effect through their ability to specifically target and then kill cancer cells. 33,34 From this, it would logically follow that individuals with increased levels of neutrophils and platelets and/or decreased levels of lymphocytes are at a higher risk of developing cancer. The results of the present analyses indicate that individuals from the general population who have higher levels of the SII at baseline are more likely to be diagnosed with a solid cancer during follow-up.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The systemic immune‐inflammation index is associated with an increased risk of incident cancer—A population‐based cohort study

Fest

Ruiter

Mulder

et al. 2019

Intl Journal of Cancer

114

103

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Several studies found that the systemic immune‐inflammation index (SII) is a prognostic factor for mortality in patients with solid tumors. It is unknown whether an increased SII in generally healthy individuals reflects a risk for developing cancer. Our objective was to investigate the association between the SII and incident cancers in a prospective cohort study. Data were obtained from the Rotterdam Study; a population‐based study of individuals aged ≥45 years, between 2002 and 2013. The SII at baseline was calculated from absolute blood counts. The association between the SII and the risk of any solid incident cancer during follow‐up was assessed using Cox proportional hazard models. Individuals with a prior cancer diagnosis were excluded. Data of 8,024 individuals were included in the analyses. The mean age at baseline was 65.6 years (SD 10.5 years) and the majority were women. During a maximum follow‐up period of 10.7 years, 733 individuals were diagnosed with cancer. A higher SII at baseline was associated with a 30% higher risk of developing a solid cancer (HR of 1.30 [95% CI; 1.11–1.53]), after adjustment for age, sex, socioeconomic status, smoking, BMI and type 2 diabetes. The absolute cumulative 10‐year cancer risk increased from 9.7% in the lowest quartile of SII to 14.7% in the highest quartile (p‐value = 0.009). The risk of developing cancer was persistent over time and increased for individuals with the longest follow‐up. In conclusion, a high SII is a strong and independent risk indicator for developing a solid cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The systemic immune‐inflammation index is associated with an increased risk of incident cancer—A population‐based cohort study

Fest

Ruiter

Mulder

et al. 2019

Intl Journal of Cancer

114

103

View full text Add to dashboard Cite

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“…10 A promising avenue in cancer therapy is the reprogramming of the TME to restore the cancer-immunity cycle and thus the body’s own defense against tumors. 11,12 …”

Section: Introductionmentioning

confidence: 99%

In Situ Vaccination with Cowpea vs Tobacco Mosaic Virus against Melanoma

et al. 2018

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Cancer immunotherapy approaches have emerged as novel treatment regimens against cancer. A particularly interesting avenue is the concept of in situ vaccination, where immunostimulatory agents are introduced into an identified tumor to overcome local immunosuppression and, if successful, mount systemic antitumor immunity. We had previously shown that nanoparticles from cowpea mosaic virus (CPMV) are highly potent in inducing long-lasting antitumor immunity when used as an in situ vaccine in various tumor mouse models. Here we asked whether the nanoparticles from tobacco mosaic virus (TMV) could also be applied as an in situ vaccine and, if so, whether efficacy or mechanism of immune-activation would be affected by the nanoparticle size (300 × 18 nm native TMV vs 50 × 18 nm short TMV nanorods), shape (nanorods vs spherical TMV, termed SNP), or state of assembly (assembled TMV rod vs free coat protein, CP). Our studies indicate that CPMV, but less so TMV, elicits potent antitumor immunity after intratumoral treatment of dermal melanoma (B16F10 using C57BL/6 mice). TMV and TMVshort slowed tumor growth and increased survival time, however, at significantly lower potency compared to that of CPMV. There were no apparent differences between TMV, TMVshort, or the SNP indicating that the aspect ratio does not necessarily play a role in plant viral in situ vaccines. The free CPs did not elicit an antitumor response or immunostimulation, which may indicate that a multivalent assembly is required to trigger an innate immune recognition and activation. Differential potency of CPMV vs TMV can be explained with differences in immune-activation: data indicate that CPMV stimulates an antitumor response through recruitment of monocytes into the tumor microenvironment (TME), establishing signaling through the IFN-γ pathway, which also leads to recruitment of tumor-infiltrated neutrophils (TINs) and natural killer (NK) cells. Furthermore, the priming of the innate immune system also mounts an adaptive response with CD4+ and CD8+ T cell recruitment and establishment of effector memory cells. While the TMV treatment also lead to the recruitment of innate immune cells as well as T cells (although to a lesser degree), key differences were noted in cyto/chemokine profiling with TMV inducing a potent immune response early on characterized by strong pro-inflammatory cytokines, primarily IL-6. Together, data indicate that some plant viral nanotechnology platforms are more suitable for application as in situ vaccines than others; understanding the intricate differences and underlying mechanism of immune-activation may set the stage for clinical development of these technologies.

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“…The expression of PD-1 on T cells is reported to inhibit glycolysis or amino acid metabolism and up-regulate fatty acid oxidation leading to impaired energy generation, which compromises proliferation and effector functions 30 . CTLA-4 can also cause decreased expression of GLUT1, increased mitochondrial oxidation and fatty acid uptake, and decreased biosynthesis on T cells 31,32 . Therefore, inhibition of PD-1/PD-L1 and CTLA-4 would preferentially promote T-cell function.…”

Section: Discussionmentioning

confidence: 99%

Detecting Early Response to Immune Checkpoint Blockade by Multimodal Molecular Imaging

Saida

Brender

Yamamoto

et al. 2020

Preprint

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Immune checkpoint inhibitors have become a standard therapy for several cancers; however, the response is inconsistent and a method for non-invasive assessment has not been established to date. To investigate the capability of multi-modal imaging to evaluate treatment response to immune checkpoint blockade therapy, we employed hyperpolarized 13 C MRI on tumor bearing mice using [1-13 C] pyruvate and [1,4-13 C2] fumarate to detect early changes in tumor glycolysis and necrosis, respectively. Following αPD-L1 Ab + αCTLA-4 Ab dual immune checkpoint blockade (ICB) therapy, dynamic contrast enhanced (DCE) MRI was used to determine the treatment effect on intratumor perfusion/permeability. Mice bearing MC38 colon adenocarcinoma and B16.F10 melanoma were used as sensitive and less sensitive models, respectively to immune checkpoint dual blockade of PD-L1 and CTLA-4. Glycolytic flux significantly decreased upon treatment in the less ICB sensitive B16.F10 model but remained essentially unchanged in MC38 tumors. Imaging [1,4-13 C] fumarate conversion to [1,[4][5][6][7][8][9][10][11][12][13] C] malate showed a significant increase in necrosis in the treatment group for the ICB sensitive MC38 tumor (p = 0.0003), with essentially no change in ICB sensitive B16.F10 tumors. Histological assessment showed increased necrotic tissue with enhanced lymphocyte infiltration in the MC38 treatment group, suggesting immunogenic tumor cell death. Dynamic contrast enhanced MRI showed significantly increased perfusion/permeability of Gd-DTPA in MC38 treated tumor, while a similar trend but statistically non-significant change was observed in B16.F10 treated tumor. These results provide imaging biomarkers to detect early response to cancer immunotherapy, allowing qualitative assessment of tumors treated with immune checkpoint blockade therapy.

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Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes

Cited by 88 publications

References 105 publications

The systemic immune‐inflammation index is associated with an increased risk of incident cancer—A population‐based cohort study

The systemic immune‐inflammation index is associated with an increased risk of incident cancer—A population‐based cohort study

In Situ Vaccination with Cowpea vs Tobacco Mosaic Virus against Melanoma

Detecting Early Response to Immune Checkpoint Blockade by Multimodal Molecular Imaging

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