PD-L1 Expression in Triple-Negative Breast Cancer

Mittendorf, Elizabeth A.; Philips, Anne V.; Meric‐Bernstam, Funda; Qiao, Na; Wu, Yun; Harrington, Susan M.; Su, Xiaoping; Wang, Ying; González-Angulo, Ana M.; Akçakanat, Argun; Chawla, Akhil; Curran, Michael A.; Hwu, Patrick; Sharma, Padmanee; Litton, Jennifer K.; Molldrem, Jeffrey J.; Alatrash, Gheath

doi:10.1158/2326-6066.cir-13-0127

Cited by 1,013 publications

(846 citation statements)

References 39 publications

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“…PD-L1 can be expressed both on tumor cells and infiltrating immune cells and may correlate with favorable prognosis and response to immune checkpoint inhibitor therapy in diverse tumor types including non-small cell lung carcinoma, melanoma, and urothelial carcinoma (10)(11)(12)(13)(14). PD-L1 expression in invasive breast carcinomas is most common in tumor cells in triple-negative cancers and correlates closely with the extent of the immune infiltrate (15,16).…”

Section: Introductionmentioning

confidence: 99%

Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features

Hendry

Pang

Byrne

et al. 2017

Clinical Cancer Research

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Purpose: The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown.Experimental Design: We quantified tumor associated lymphocytes (TIL) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases, respectively), some of which had copy number (n ¼ 55) and mutation data (n ¼ 20).Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range, 0%-90%). Most DCIS were negative for tumor cell PD-L1 staining (89%), but 25% of cases were positive for immune cell staining. We observed that, as in invasive breast cancer, TILs and PD-L1 positivity were significantly greater in high-grade (P ¼ 0.002/0.035), ER-negative (P ¼ 0.02/0.02), and ERBB2-amplified tumors (P < 0.001/0.048). Comedo necrosis was significantly positively associated with TILs (P < 0.0001) but not with PD-L1. The TILs score was significantly higher in cases with TP53 mutation (P ¼ 0.03) but not with PIK3CA or GATA3 mutation. In the cases with copy number data, both the fraction of the genome altered and the number of telomeric imbalances were significantly positively correlated with TILs (both P < 0.001). This result strongly contrasted with invasive breast cancer data, where aneuploidy was not correlated to TIL levels.Conclusions: Although a small cohort, our data suggest a preliminary model by which the progression of DCIS to invasive carcinoma may involve an altered relationship of tumor copy number with the immune microenvironment, possibly by the immunoediting of the tumor. Clin Cancer Res; 23(17); 5210-7.Ó2017 AACR.

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Section: Introductionmentioning

confidence: 99%

Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features

Hendry

Pang

Byrne

et al. 2017

Clinical Cancer Research

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“…This is believed to be important to cytological study from the point of the purification of monoclonal cells of cell lines (9,10). In order to obtain monoclonal stem cell samples from MG63 cells, the cloned cells densely distributed in a round or oval shape were selected, which have the ability to form tumors.…”

Section: A B C D E F Discussionmentioning

confidence: 99%

Programmed cell death 1 correlates with the occurrence and development of MG63 osteosarcoma

Zhao

Dai

et al. 2016

Oncology Letters

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Abstract. The aim of the present study was to investigate the effect of programmed cell death 1 (PD-1) on osteosarcoma (OD) stem cells and T cells, and to determine their correlation. OS stem cells were sorted and identified from OS MG63 cells. Flow cytometry was used to detect the PD-1 expression of the OS tumor stem cell membrane surface. The expression of PD-1 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). MTT was used to detect the effect of PD-1 signals on T-cell proliferation. The results indicated that the cancer cells (cultured in DMEM medium containing 10% fetal bovine serum) exhibited clear proliferation within 1 week of cell culture, which showed their strong proliferation and aggressive ability. The formation of tumor cell spheres was dependent on the support of serum nutrition. The proliferation of MG63 cells in the serum culture medium was significantly higher than the number of OS cell spheres in serum-free suspension culture (P<0.05). Pluripotent stem cells in cancer cell spheres exhibited significantly higher cluster of differentiation 133 expression compared with the MG63 cells. The PD-1 expression levels of the cancer cell spheres was significantly increased compared with the MG63 cells, which is consistent with the results of the RT-PCR. In conclusion, the MG63 cell line possesses the features of OS stem cells. The MG63 cell line can express the certain cancer-associated cell markers. The expression of PD-1 in spheres was also increased significantly compared to the MG63 cells, which can reduce the immune function of patients and may be closely associated with the occurrence and development of tumors.

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“…In general, TNBCs have a higher density of TILs, more active expression of inlammatoryrelated genes, and considering that the prognostic role of TILs is more prominent in TNBC than in other subtypes, the eicacy of PD1 inhibition has so far been evaluated in this seting [58,59]. Results from two studies assessing the anti-PD1 mAb pembrolizumab and the anti-PDL1 atezolizumab were recently presented.…”

Section: Immunotherapy In Breast Cancermentioning

confidence: 99%

Immune Regulation in Breast Cancer Metastasis and Immunotherapy

Dai¹

2017

Breast Cancer - From Biology to Medicine

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There are signiicant alterations in the tumor surrounding stromal cells in addition to the cancer cells in tumor microenvironment. Tumor cells can metastasize by acquiring the ability to escape immune control and surveillance. A decline in the ability of the immune cells to recognize and kill the tumor leads to tumor relapse or metastasis after primary treatment. Comprehensive review in this chapter will be conducted to further investigate into the mechanism of immune evasion in metastatic tumor microenvironment. The immune cells, stromal cells, extracellular matrix protein/component, and their interaction will be reviewed and summarized. Breast cancer has not been previously viewed as a particularly immunogenic type of tumor. Nevertheless, immune parameters have been increasingly studied in breast cancer, and accumulating data show that they are relevant for the development and progression of this tumor type. Consequently, immunotherapies of breast cancer are now tested in diferent clinical trials. The prospect of immunotherapy in metastatic breast cancer will be introduced. The importance of host-targeted modulation/therapy will be increased in addition to cancer-targeted strategies. We have to beter deine subpopulations of breast cancer patients to optimize the immunological way to overcome the cancer metastasis.

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PD-L1 Expression in Triple-Negative Breast Cancer

Cited by 1,013 publications

References 39 publications

Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features

Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features

Programmed cell death 1 correlates with the occurrence and development of MG63 osteosarcoma

Immune Regulation in Breast Cancer Metastasis and Immunotherapy

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