Expression of PD-1/PD-L1 in primary breast tumours and metastatic axillary lymph nodes and its correlation with clinicopathological parameters

Yuan, Chenxi; Liu, Zhaoyun; Yu, Qian; Wang, Xinzhao; Bian, Mengxue; Yu, Zhiyong; J, Yu

doi:10.1038/s41598-019-50898-3

Cited by 66 publications

(45 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These preliminary results justified closer examination of this pathway and its potential therapeutic role in CSCC. Some studies demonstrated the presence of cell surface PD-1/PD-L1 in human tumors, and this expression has been linked to poor clinical outcomes in a variety of cancers [112][113][114][115][116], including CSCC [117,118]. CSCC has the highest mutational burden of all tumors, and is a good candidate for immunotherapy treatment [21].…”

Section: Immunotherapy In Csccmentioning

confidence: 99%

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

Corchado-Cobos

García-Sancha

González-Sarmiento

et al. 2020

IJMS

135

111

View full text Add to dashboard Cite

Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and its incidence continues to rise. Although CSCC usually display a benign clinical behavior, it can be both locally invasive and metastatic. The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades. In addition, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape. This review focuses on the molecular basis of CSCC and the current biology-based approaches of targeted therapies and immune checkpoint inhibitors. Another purpose of this review is to explore the landscape of drugs that may induce or contribute to the development of CSCC. Beginning with the pathogenetic basis of these drug-induced CSCCs, we move on to consider potential therapeutic opportunities for overcoming this adverse effect.

show abstract

Section: Immunotherapy In Csccmentioning

confidence: 99%

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

Corchado-Cobos

García-Sancha

González-Sarmiento

et al. 2020

IJMS

135

111

View full text Add to dashboard Cite

show abstract

“…Up to 30.7% of PD-1 expression on tumor-infiltrating lymphocytes (TILs) around HER2 + BC is also seen. PD-1/PD-L1 expression in metastatic tumors was correlated with poor prognosis, whereas no relation to clinicopathological features was noted in primary tumors [109]. In essence, it can be seen from literature that high PD-L1 expression combined with an increase in T regulatory cells (Tregs) and a decrease of TILs are associated with poor survival [22,102,107,110].…”

Section: Pd-1/pd-l1 and Her2 Crosstalk In Breast Cancermentioning

confidence: 99%

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Padmanabhan

Kheraldine

Meskin

et al. 2020

Cancers

View full text Add to dashboard Cite

Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.

show abstract

“…It is known that tumor cells express programmed death-ligand 1 (PD-L1) that binds PD-1 on T cell, resulting in dysfunction of cytotoxic T-cell activity [45]. Several other studies have also shown that microglia expresses PD-L1, which interacts with T cell PD-1 to suppress adaptive immune function and tumor in ltration of T cells [45][46][47]. We therefore examined whether E2 affects PD-L1 expression in microglia.…”

Section: Estrogen Suppressed Anti-tumor Immune Function Of Microgliamentioning

confidence: 99%

Tamoxifen Suppresses Brain Metastasis of Estrogen Receptor-deficient Breast Cancer by Skewing Microglia Polarization and Enhancing Their Immune Functions

Sharma

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Brain metastasis of breast cancer exhibits exceedingly poor prognosis, and both triple negative and Her2+ subtypes have the highest incidence of brain metastasis. Although estrogen blockers are considered to be ineffective for their treatment, recent evidences indicate that estrogen blockade using tamoxifen showed certain efficacy. However, how estrogen affects brain metastasis of triple negative breast cancer (TNBC) remains elusive. Methods: To examine the effect of estrogen on brain metastasis progression, nude mice were implanted with brain metastatic cells and treated with either estrogen supplement, tamoxifen or ovariectomy for estrogen depletion. For clinical validation study, brain metastasis specimens from pre- and post-menopause breast cancer patients were examined for microglia polarization by immunohistochemistry. To examine the estrogen-induced M2 microglia polarization, microglia cells were treated with estrogen and the M1/M2 microglia polarization was detected by qRT-PCR and FACS. The estrogen receptor-deficient brain metastatic cells, SkBrM and 231BrM, were treated with conditioned medium (CM) derived from microglia that were treated with estrogen in the presence or absence of tamoxifen. The effect of microglia-derived CMs on tumor cells was examined by colony formation assay and sphere forming ability. Results: We found that M2 microglia were abundantly infiltrated in brain metastasis of pre-menopausal breast cancer patients. A similar observation was made in vivo, when we treated mice systemically with estrogen. Blocking of estrogen signaling either by tamoxifen treatment or surgical resection of mice ovaries suppressed M2 microglial polarization and decreased the secretion of C-C motif chemokine ligand 5, resulting in suppression of brain metastasis. The estrogen modulation also suppressed stemness in TNBC cells in vitro. Importantly, estrogen enhanced the expression of signal regulatory protein α on microglia and restricted their phagocytic ability. Conclusions: Our results indicate that estrogen promotes brain metastasis by skewing polarity of M2 microglia and inhibiting their phagocytic ability, while tamoxifen suppresses brain metastasis by blocking the M2 polarization of microglia and increasing their anti-tumor phagocytic ability. Our results also highlight a potential therapeutic utility of tamoxifen for treating brain metastasis of hormone receptor deficient breast cancer.

show abstract

Expression of PD-1/PD-L1 in primary breast tumours and metastatic axillary lymph nodes and its correlation with clinicopathological parameters

Cited by 66 publications

References 31 publications

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Tamoxifen Suppresses Brain Metastasis of Estrogen Receptor-deficient Breast Cancer by Skewing Microglia Polarization and Enhancing Their Immune Functions

Contact Info

Product

Resources

About