scholarly journals MuTILs: explainable, multiresolution computational scoring of Tumor-Infiltrating Lymphocytes in breast carcinomas using clinical guidelines

2022 ◽  
Author(s):  
Mohamed Amgad ◽  
Roberto Salgado ◽  
Lee A.D. Cooper
Keyword(s):  
Network Architecture ◽  
Tumor Infiltrating Lymphocytes ◽  
Visual Assessment ◽  
Breast Cancers ◽  
Neural Network Architecture ◽  
Slide Image ◽  
Multiple Resolutions ◽  
Clinical Scoring ◽  
Tcga Dataset ◽  
Infiltrating Lymphocytes

Tumor-Infiltrating Lymphocytes (TILs) have strong prognostic and predictive value in breast cancer, but their visual assessment is subjective. We present MuTILs, a convolutional neural network architecture specifically optimized for the assessment of TILs in whole-slide image scans in accordance with clinical scoring recommendations. MuTILs is a concept bottleneck model, designed to be explainable and to encourage sensible predictions at multiple resolutions. Our computational scores match visual scores and have independent prognostic value in invasive breast cancers from the TCGA dataset.

Metaplastic breast cancers: Genomic profiling, mutational burden and tumor-infiltrating lymphocytes

The Breast ◽  
2019 ◽  
Vol 44 ◽  
pp. 29-32 ◽  
Author(s):  
Nancy Tray ◽  
Jessica Taff ◽  
Baljit Singh ◽  
James Suh ◽  
Nhu Ngo ◽  
...  
Keyword(s):  
Tumor Infiltrating Lymphocytes ◽  
Genomic Profiling ◽  
Breast Cancers ◽  
Mutational Burden ◽  
Infiltrating Lymphocytes

scholarly journals Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pre- and Posttreatment Breast Cancers in the SWOG S0800 Phase II Neoadjuvant Chemotherapy Trial

2018 ◽  
Vol 17 (6) ◽  
pp. 1324-1331 ◽  
Author(s):  
Vasiliki Pelekanou ◽  
William E. Barlow ◽  
Zeina A. Nahleh ◽  
Brad Wasserman ◽  
Ying-Chun Lo ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancers ◽  
Infiltrating Lymphocytes

scholarly journals Immunotherapeutic Approaches in Triple-Negative Breast Cancer: State of the Art and Future Perspectives

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Karima Oualla ◽  
Loay Kassem ◽  
Lamiae Nouiakh ◽  
Lamiae Amaadour ◽  
Zineb Benbrahim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Poor Outcomes ◽  
Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It accounts for 15%–20% of all breast cancers and is associated with an aggressive evolution and poor outcomes with the majority of recurrences and deaths occurring in the first 5 years. Chemotherapy remains the mainstay of treatment in the absence of effective targets, but the good understanding of immune tumor microenvironment, the identification of immune-related targets, and the role of tumor-infiltrating lymphocytes (TILs) in TNBC has allowed to develop promising immunotherapeutic strategies for this unique subset of breast cancer. Recently, immunotherapy is being extensively explored in TNBC and clinical trials have shown promising results. In this article, we tried to explain the rationale and mechanisms of targeting the immune system in TNBC, to report the results from recent clinical trials that put immunotherapy as a new standard of care in TNBC in addition to ongoing trials and future directions in the next decade.

scholarly journals Association between levels of tumor-infiltrating lymphocytes in different subtypes of primary breast tumors and prognostic outcomes: a meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lin He ◽  
Yaling Wang ◽  
Qian Wu ◽  
Yuhua Song ◽  
Xuezhen Ma ◽  
...  
Keyword(s):  
Molecular Subtypes ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Tumors ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Tumor Subtype ◽  
Luminal Tumor ◽  
High Level ◽  
Infiltrating Lymphocytes

Abstract Background To investigate the impact of the elevation of tumor-infiltrating lymphocytes (TILs) in different molecular subtypes of primary breast cancer, i.e. each 10% increment of TILs and high-level TILs (TILs≥50%) in tumor, on overall survival (OS) and pathological complete response (pCR) and to compare the presentation of high-level TILs across these molecular subtypes. Methods Citation retrieval was performed in the PubMed, Cochrane Library, Embase and Web of Science databases. All statistical calculations were performed by the software of StataSE version 12.0. Results Twenty-two eligible clinical trials including 15,676 unique patients were included for meta-analysis. Each 10% increment of TILs significantly improved OS in human epidermal growth factor receptor 2 (HER2)-overexpression (pooled Hazard ratio (HR), 0.92; 95% CI, 0.89–0.95) and triple-negative (TN) (pooled HR, 0.90; 95% CI, 0.89–0.92) breast tumors but not in luminal tumor subtype (pooled HR, 1.06; 95% CI, 0.99–1.13). It was also associated with an increased pCR rate in breast cancers (pooled Odds ratio (OR), 1.27; 95% CI, 1.19–13.5). High-level TILs were significantly related with a higher pCR rate (pooled OR, 2.73; 95% CI, 2.40–3.01) than low-level TILs. The HER2-amplified (pooled OR, 3.14; 95% CI, 1.95–5.06) and TN (pooled OR, 4.09; 95% CI, 2.71–6.19) phenotypes of breast cancers expressed significantly more high-level TILs than the luminal tumor subtype, although the presentation of those between the former two subsets was not significantly different (pooled OR, 1.30; 95%CI, 0.83–2.04). Conclusions The elevation of TILs in breast tumors predicts favorable prognostic outcomes, particularly in the HER2-overexpression and TN subtypes.

scholarly journals Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yeon Hee Park ◽  
Samir Lal ◽  
Jeong Eon Lee ◽  
Yoon-La Choi ◽  
Ji Wen ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Pathologic Complete Response ◽  
Tumor Infiltrating Lymphocytes ◽  
Transcriptome Profiling ◽  
Complete Response ◽  
Strongly Correlated ◽  
Breast Cancers ◽  
Breast Cancer Cohort ◽  
Tumor Biopsies ◽  
Infiltrating Lymphocytes

AbstractTo elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.

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