Hypoxia and anaerobic metabolism relate with immunologically cold breast cancer and poor prognosis

Giatromanolaki, Alexandra; Gkegka, Anastasia G; Pouliliou, Stamatia; Biziota, Eirini; Kakolyris, Stylianos; Koukourakis, Michael I.

doi:10.1007/s10549-022-06609-0

Cited by 19 publications

(20 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation is explained by the well-known adverse effects of hypoxia and acidity on lymphocyte survival and proliferation [ 14 , 15 ]. Our group has confirmed a similar association in breast and lung cancer studies [ 22 , 34 ]. The pharmacological blockage of HIF or CA9 with specific inhibitors to transform the cold immune environment of such HIF-driven tumors could eventually have therapeutic implications in cancer immunotherapy.…”

Section: Discussionsupporting

confidence: 90%

“…The methodology applied for quantifying TILs in H&E cancer tissue sections varies among researchers. The density of lymphocytes can be assessed in different tumor areas, such as invading front, inner stroma areas or even cancer cell nests (intra-epithelial lymphocytes) [ 20 , 21 , 22 ]. The assessment of TILs in these distinct cancer tissue areas often shows different prognostic correlations.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy

et al. 2022

Self Cite

View full text Add to dashboard Cite

Microenvironmental conditions control the entrance and thriving of cytotoxic lymphocytes in tumors, allowing or preventing immune-mediated cancer cell death. We investigated the role of tumor-infiltrating lymphocyte (TIL) density in the outcome of radiotherapy in a series of squamous cell head–neck tumors (HNSCC). Moreover, we assessed the link between markers of hypoxia and TIL density. One-hundred twenty-one patients with HNSCC treated prospectively with radical radiotherapy/chemo-radiotherapy were analyzed. The assessment of TIL density was performed on hematoxylin and eosin biopsy sections before radiotherapy. TIL density ranged from 0.8 to 150 lymphocytes per ×40 optical field (median 27.5). Using the median value, patients were grouped into two categories of low and high TIL density. Early T-stage tumors had a significantly higher TIL density (p < 0.003), but we found no association with N-stage. Overexpression of HIF1α, HIF2α, and CA9 was significantly linked with poor infiltration by TILs (p < 0.03). A significant association of high TIL density with better disease-specific overall survival and improved locoregional relapse-free survival was noted (p = 0.008 and 0.02, respectively), which was also confirmed in multivariate analysis. It is concluded that HNSCC phenotypes that allow for the intratumoral accumulation of lymphocytes have a better outcome following radical radiotherapy/chemo-radiotherapy. Intratumoral-activated HIF- and CA9-related pathways characterize immunologically cold tumors and may be used as targets for therapeutic interventions.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…In BC cells, hypoxia induces the expression of BIRC2, which counters the capability of CXCL9 to recruit CD8+ T cells and NK cells to the tumor, and hence increases tumor growth and resistance to anti-PD-1 therapy [ 116 ]. In hypoxic BC cells, the HIF-1 transcription factor is activated together with anaerobic metabolism and lactate dehydrogenase (LDHA) production [ 117 ]. The expression of both HIF1α and LDH5 defines “cold”, immunologically silent BCs and poor prognosis of patients [ 117 ].…”

Section: Impact Of Abnormal Breast Tumor Vascular On Immune Cellsmentioning

confidence: 99%

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

Melaiu

Vanni

Portarena

et al. 2023

IJMS

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients.

show abstract

“…Additionally, tumor-associated and/or therapy-induced anaemia reduces the blood's ability to carry oxygen, which results in hypoxia in tumor areas [74]. Poor prognosis, radiotherapy/chemotherapy resistance, and tumor metastasis are all linked to hypoxia [75]. Tumor cells can adapt to hypoxic conditions by producing erythropoietin (EPO), switching from aerobic to anaerobic metabolism, downregulating DNA repair pathways, enlisting the assistance of stromal cells, and upregulating protooncogenes as well as hypoxia-inducible factor (HIF) 1 and HIF 2 [76].…”

Section: Targeting Hypoxiamentioning

confidence: 99%

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

Mbugua

2022

Bioinorganic Chemistry and Applications

View full text Add to dashboard Cite

Solid tumors have a unique tumor microenvironment (TME), which includes hypoxia, low acidity, and high hydrogen peroxide and glutathione (GSH) levels, among others. These unique factors, which offer favourable microenvironments and nourishment for tumor development and spread, also serve as a gateway for specific and successful cancer therapies. A good example is metal peroxide structures which have been synthesized and utilized to enhance oxygen supply and they have shown great promise in the alleviation of hypoxia. In a hypoxic environment, certain oxygen-dependent treatments such as photodynamic therapy and radiotherapy fail to respond and therefore modulating the hypoxic tumor microenvironment has been found to enhance the antitumor impact of certain drugs. Under acidic environments, the hydrogen peroxide produced by the reaction of metal peroxides with water not only induces oxidative stress but also produces additional oxygen. This is achieved since hydrogen peroxide acts as a reactive substrate for molecules such as catalyse enzymes, alleviating tumor hypoxia observed in the tumor microenvironment. Metal ions released in the process can also offer distinct bioactivity in their own right. Metal peroxides used in anticancer therapy are a rapidly evolving field, and there is good evidence that they are a good option for regulating the tumor microenvironment in cancer therapy. In this regard, the synthesis and mechanisms behind the successful application of metal peroxides to specifically target the tumor microenvironment are highlighted in this review. Various characteristics of TME such as angiogenesis, inflammation, hypoxia, acidity levels, and metal ion homeostasis are addressed in this regard, together with certain forms of synergistic combination treatments.

show abstract

Hypoxia and anaerobic metabolism relate with immunologically cold breast cancer and poor prognosis

Cited by 19 publications

References 44 publications

Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy

Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

Contact Info

Product

Resources

About