CD73 expression and pathologic response to neoadjuvant chemotherapy in triple negative breast cancer

Cerbelli, Bruna; Botticelli, Andrea; Pisano, Annalinda; Pernazza, Angelina; Campagna, Domenico; Luca, Alessandro De; Ascierto, Paolo A.; Pignataro, Maria Gemma; Pelullo, Maria; Rocca, Carlo Della; Marchetti, Paolo; Fortunato, Lucio; Costarelli, Leopoldo; d’Amati, Giulia

doi:10.1007/s00428-019-02722-6

Cited by 21 publications

(16 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with this, in a recent study (2019), Cerbelli et al showed the potential of CD37 expression and TILs to predict response to NAC in a TN cohort ( n = 61). Both the presence of TILs and CD37 expression were associated with a better pCR rate ( p = 0.037, univariate; p = 0.011 and p = 0.014, univariate and multivariate, respectively) [ 40 ]. Taking into consideration not only these associations of tumor microenvironment-specific features with pCR, but also the groundbreaking therapies based on reactivation of tumor immune suppression in the exhausted inflamed tumor scenario, we anticipate that tumor-associated lymphocytes will be key for the assessment of response to neoadjuvant therapeutic approaches.…”

Section: Predictive Factors Of Pathological Complete Responsementioning

confidence: 99%

Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

Chica-Parrado

Godoy-Ortiz

Jiménez

et al. 2020

Cancers

View full text Add to dashboard Cite

Neoadjuvant Chemotherapy (NAC) in Breast Cancer (BC) has proved useful for the reduction in tumor burden prior to surgery, allowing for a more extensive breast preservation and the eradication of subjacent micrometastases. However, the impact on prognosis is highly dependent on the establishment of Pathological Complete Response (pCR), in particular for Triple Negative (TN) and Hormonal Receptor negative/Human Epidermal growth factor Receptor 2 positive (HR−/HER2+) subtypes. Several pCR predictors, such as PAM50, Integrative Cluster (IntClust), mutations in PI3KCA, or the Trastuzumab Risk model (TRAR), are useful molecular tools for estimating response to treatment and are prognostic. Major evolution events during BC NAC that feature the Residual Disease (RD) are the loss of HR and HER2, which are prognostic of bad outcome, and stemness and immune depletion-related gene expression aberrations. This dynamic nature of the determinants of response to BC NAC, together with the extensive heterogeneity of BC, raises the need to discern the individual and subtype-specific determinants of resistance. Moreover, refining the current approaches for a comprehensive monitoring of tumor evolution during treatment, RD, and eventual recurrences is essential for identifying new actionable alterations and the integral best management of the disease.

show abstract

Section: Predictive Factors Of Pathological Complete Responsementioning

confidence: 99%

Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

Chica-Parrado

Godoy-Ortiz

Jiménez

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…In the context of novel biomarkers, indoleamine 2,3-dioxygenase (IDO) [ 32 , 33 ], the enzymes family involved in tryptophan catabolism, CD73, an immunosuppressive ecto-enzyme involved in the production of adenosine [ 34 , 35 , 36 , 37 , 38 ], and microbiome [ 39 , 40 , 41 ] seem to have a promising role. The complete and comprehensive immune profile requires simultaneous and dynamic evaluation of many biomarkers that cooperate for the success or failure of the immune response, rather than research on a single biomarker.…”

Section: Introductionmentioning

confidence: 99%

The Agnostic Role of Site of Metastasis in Predicting Outcomes in Cancer Patients Treated with Immunotherapy

et al. 2020

Self Cite

View full text Add to dashboard Cite

Immune checkpoint inhibitors have revolutionized treatment and outcome of melanoma and many other solid malignancies including non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Unfortunately, only a minority of patients have a long-term benefit, while the remaining demonstrate primary or acquired resistance. Recently, it has been demonstrated that the prevalence of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) varies based on the anatomical site of metastases. In particular, liver seems to have more immunosuppressive microenvironment while both the presence of lymph nodal disease and lung metastases seem to have the highest prevalence of PD-L1 and TILs. The aim of the present study is to investigate the possible role of site of metastases as a predictive factor for response or resistance to immunotherapy in several types of cancer. In this multicenter retrospective study, we enrolled patients with metastatic NSCLC, melanoma, RCC, urothelial, merkel carcinoma, and colon cancer who received immunotherapy from April 2015 to August 2019. Major clinicopathological parameters were retrieved and correlated with patients’ survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision-making process. A total of 291 patients were included in this study. One hundred eighty-seven (64%) patients were male and 104 (36%) female. The tumor histology was squamous NSCLC in 56 (19%) patients, non-squamous NSCLC in 99 (34%) patients, melanoma in 101 (35%) patients, RCC in 28 (10%) patients, and other tumors in the remaining 7 (2%) patients. The number of metastatic sites was 1 in 103 patients (35%), 2 in 104 patients (36%) and 3 in 84 patients (29%). Out of 183 valuable patients, the entity of response was complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD) in 15, 53, 31, and 79 patients, respectively. Using an univariate analysis (UVA), tumor burden (p = 0.0004), the presence of liver (p = 0.0009), bone (p = 0.0016), brain metastases (p < 0.0001), the other metastatic sites (p = 0.0375), the number of metastatic sites (p = 0.0039), the histology (p = 0.0034), the upfront use of immunotherapy (p = 0.0032), and Eastern Cooperative Oncology Group (ECOG) Perfomance status (PS) ≥ 1 (p < 0.0001) were significantly associated with poor overall survival (OS). Using a multivariate analysis (MVA) the presence of liver (p = 0.0105) and brain (p = 0.0026) metastases, the NSCLC diagnosis (p < 0.0001) and the ECOG PS (p < 0.0001) resulted as significant prognostic factors of survival. Regarding the progression free survival (PFS), using a UVA of the tumor burden (p = 0.0004), bone (p = 0.0098) and brain (p = 0.0038) metastases, the presence of other metastatic sites (p = 0.0063), the number of metastatic sites (p = 0.0007), the histology (p = 0.0007), the use of immunotherapy as first line (p = 0.0031), and the ECOG PS ≥ 1 (p ≤ 0.0001) were associated with a lower PFS rate. Using an MVA, the presence of brain (p = 0.0088) and liver metastases (p = 0.024) and the ECOG PS (p < 0.0001) resulted as predictors of poor PFS. Our study suggests that the site of metastases could have a role as prognostic and predictive factor in patients treated with immunotherapy. Indeed, regardless of the histology, the presence of liver and brain metastases was associated with a shorter PFS and OS, but these results must be confirmed in further studies. In this context, a deep characterization of microenvironment could be crucial to prepare patients through novel strategies with combination or sequential immunotherapy in order to improve treatment response.

show abstract

“…Unfortunately, only PD-L1 expression is currently used in our clinical practice, so lack of biomarkers led us to better consider the clinical features to guide the choice of strategy ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Anti–PD-1 and Anti–PD-L1 in Head and Neck Cancer: A Network Meta-Analysis

et al. 2021

Self Cite

View full text Add to dashboard Cite

ObjectiveThe monoclonal antibodies anti-programmed death protein-1 (anti–PD-1) nivolumab and pembrolizumab are the first immune checkpoint inhibitors (ICIs) approved for treatment of recurrent/metastatic head and neck carcinoma R/M HNSCC in first line and in platinum refractory disease. This network meta-analysis aims to investigate the efficacy of anti–PD-1- vs anti–PD-L1-based therapy in R/M HNSCC cancer patients through a systematic review of the literature to provide support for evidence-based treatment decisions. In particular, the effectiveness of ICIs for R/M HNSCC is analyzed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.MethodsWe did a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in PubMed, ClinicalTrials.gov, Embase, Medline, the Cochrane Central Register of Controlled Trials, Web of Science. Our search identified a total of five randomized controlled trials: Keynote 040, Keynote 048, Eagle, Condor, Checkmate 141. These trials included 3001 patients. Treatment was sub-categorized into PD-L1–based, PD-1–based, and standard chemotherapy. Treatments were indirectly compared with anti–PD-L1-based therapy.ResultsThe network meta-analysis demonstrated no significant differences in OS between different subgroups except for the metastatic patients in which anti–PD-1-based therapy was associated with significantly less risk of death. Furthermore, anti–PD-1-based therapy appeared to be effective in smoker patients and in human papilloma–negative (HPV) patients. Conversely, anti–PD-L1-based therapy seems to be better efficient in female patients, in locally recurrent setting and in HPV positive patients.ConclusionThis is the first NMA study that aimed to indirectly compare anti–PD-1- and anti–PD-L1-based therapy in HNSCC patients. The results of our NMA could help define a profile of patient responder or resistant to specific classes of immune drugs and can be used to guide/design future studies in the novel scenario of precision immune-oncology.

show abstract

CD73 expression and pathologic response to neoadjuvant chemotherapy in triple negative breast cancer

Cited by 21 publications

References 43 publications

Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

The Agnostic Role of Site of Metastasis in Predicting Outcomes in Cancer Patients Treated with Immunotherapy

Anti–PD-1 and Anti–PD-L1 in Head and Neck Cancer: A Network Meta-Analysis

Contact Info

Product

Resources

About