PD-L1 Expression and Intratumoral Heterogeneity Across Breast Cancer Subtypes and Stages

Dill, Erik; Gru, Alejandro A.; Atkins, Kristen A.; Friedman, Lisa Aronson; Moore, Margaret E.; Bullock, Timothy N. J.; Cross, Janet V.; Dillon, Patrick M.; Mills, Anne M.

doi:10.1097/pas.0000000000000780

Cited by 149 publications

(146 citation statements)

References 33 publications

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“…In addition, it has been reported that PD‐L1 is differentially expressed across different BC subtypes. In particular, available evidence consistently reports greater expression of PD‐L1 in the TN subtype (up to 60% of PD‐L1 expression) compared with non‐TNBC . These data appear to be coherent with the observation that PD‐L1 tumor expression is positively associated with stromal tumor‐infiltrating lymphocytes (TILs) in this BC subtype , which is known to be more frequently infiltrated by stromal TILs than non‐TNBC , as summarized in Table , thus possibly suggesting that these two immune biomarkers tend to run parallel.…”

Section: Methodssupporting

confidence: 74%

“…Data on PD‐L1 expression in HER2‐positive BC are more controversial. In fact, whereas in some studies HER2 positivity has been correlated with higher expression of PD‐L1 (up to 50%) compared with HER2‐negative BC , others failed to report any difference .…”

Section: Methodsmentioning

confidence: 93%

“…In contrast to NSCLC, where regulatory approval for anti‐PD1/PD‐L1 therapy (pembrolizumab) is based on PD‐L1 positivity assessed on tumor cells , in BC, PD‐L1 seems to be predominantly expressed by stromal compartment . However, so far, no consistent data exist on the possible biological and clinical implications of a differential expression of PD‐L1 by either tumor cells or tumor‐infiltrating immune cells.…”

Section: Methodsmentioning

confidence: 99%

“…However, so far, no consistent data exist on the possible biological and clinical implications of a differential expression of PD‐L1 by either tumor cells or tumor‐infiltrating immune cells. Of note, it has been suggested that a significant proportion of PD‐L1‐negative tumors assessed on tumor cells may actually be classified as PD‐L1 positive if assessed on stromal immune cells, thus enriching the subset of patients that might be candidates for immunotherapy . However, Tawfik and colleagues also suggested that the adoption of a stricter cutoff for PD‐L1 positivity (10% instead of 1%) may help increase the agreement between stromal and tumor compartments .

In contrast to NSCLC, where regulatory approval for anti‐PD1/PD‐L1 therapy (pembrolizumab) is based on PD‐L1 positivity assessed on tumor cells, in BC, PD‐L1 seems to be predominantly expressed by stromal compartment.…”

Section: Methodsmentioning

confidence: 99%

“…In more detail, higher concordance rates between primary and secondary lesions have been reported when PD‐L1 was assessed on tumor cells rather than on TILs . In addition, several authors reported that discordant cases in terms of PD‐L1 status between primary and secondary lesions (encompassing both distant and local lymph node metastases) tended to exhibit a gain in PD‐L1 expression rather than a loss . Finally, it has been reported that patients with TNBC with PD‐L1 gain from primary to paired local lymph node metastasis experienced worse DFS compared with patients with PD‐L1 negativity in both primary tumor and lymph node metastasis .…”

Section: Methodsmentioning

confidence: 99%

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Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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In the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple‐negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD‐L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical utility of PD‐L1 expression in BC, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker. Implications for Practice In the light of the promising results coming from trials of immune checkpoint inhibitors for breast cancer treatment, the potential predictive and/or prognostic role of programmed cell death ligand 1 (PD‐L1) in breast cancer has gained increasing interest. This review provides clinicians with an overview of the available clinical evidence regarding PD‐L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD‐L1 implementation as a clinically useful tool for breast cancer management.

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Section: Methodssupporting

confidence: 74%

Section: Methodsmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses

et al. 2019

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BackgroundFor the advancement of cancer research, the collection of tissue specimens from drug‐resistant tumors after targeted therapy is crucial. Although patients with lung cancer are often provided targeted therapy, post‐therapy specimens are not routinely collected due to the risks of collection, limiting the study of targeted therapy resistance mechanisms. Posthumous rapid tissue donation (RTD) is an expedient collection process that provides an opportunity to understand treatment‐resistant lung cancers.MethodsConsent to participate in the thoracic RTD protocol was obtained during patient care. When death occurred, tumor and paired non‐tumor, cytology, and blood specimens were collected within 48 hours and preserved as formalin‐fixed and frozen specimens. Tissue sections were evaluated with hematoxylin and eosin staining and immunohistochemistry (IHC) against multiple biomarkers, including various programmed death ligand 1 (PD‐L1) clones. Next‐generation sequencing was performed on 13 specimens from 5 patients.ResultsPostmortem specimens (N = 180) were well preserved from 9 patients with lung cancer. PD‐L1 IHC revealed heterogeneity within and between tumors. An AGK‐BRAF fusion was newly identified in tumor from a donor with a known echinoderm microtubule‐associated protein‐like 4 to anaplastic lymphoma kinase (EML4‐ALK) fusion and history of anaplastic lymphoma kinase (ALK) inhibitor therapy. RNA expression analysis revealed a clonal genetic origin of metastatic cancer cells.ConclusionsPost‐therapy specimens demonstrated PD‐L1 heterogeneity and an acyl glycerol kinase to B‐rapidly accelerated fibrosarcoma (AGK‐BRAF) fusion in a patient with an EML4‐ALK–positive lung adenocarcinoma as a potential resistance mechanism to ALK inhibitor therapy. Rapid tissue donation collection of postmortem tissue from lung cancer patients is a novel approach to cancer research that enables studies of molecular evolution and drug resistance.

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Amino acids and their roles in tumor immunotherapy of breast cancer

Xia,

Zhu,

Zheng

et al. 2023

The Journal of Gene Medicine

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Breast cancer is the most commonly diagnosed cancer among women. The primary treatment options include surgery, radiotherapy, chemotherapy, targeted therapy and hormone therapy. The effectiveness of breast cancer therapy varies depending on the stage and aggressiveness of the cancer, as well as individual factors. Advances in early detection and improved treatments have significantly increased survival rates for breast cancer patients. Nevertheless, specific subtypes of breast cancer, particularly triple‐negative breast cancer, still lack effective treatment strategies. Thus, novel and effective therapeutic targets for breast cancer need to be explored. As substrates of protein synthesis, amino acids are important sources of energy and nutrition, only secondly to glucose. The rich supply of amino acids enables the tumor to maintain its proliferative competence through participation in energy generation, nucleoside synthesis and maintenance of cellular redox balance. Amino acids also play an important role in immune‐suppressive microenvironment formation. Thus, the biological effects of amino acids may change unexpectedly in tumor‐specific or oncogene‐dependent manners. In recent years, there has been significant progress in the study of amino acid metabolism, particularly in their potential application as therapeutic targets in breast cancer. In this review, we provide an update on amino acid metabolism and discuss the therapeutic implications of amino acids in breast cancer.

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PD-L1 Expression and Intratumoral Heterogeneity Across Breast Cancer Subtypes and Stages

Cited by 149 publications

References 33 publications

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

A community‐based lung cancer rapid tissue donation protocol provides high‐quality drug‐resistant specimens for proteogenomic analyses

Amino acids and their roles in tumor immunotherapy of breast cancer

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