Tumor-Infiltrating lymphocytes (TILs) in early breast cancer patients: high CD3+ , CD8+ , and Immunoscore are associated with a pathological complete response

BACKGROUND : Tumor-infiltrating lymphocytes are associated with a better prognosis in early triple-negative breast cancer (TNBC). These cells can be enumerated in situ by the “Immunoscore Clinical Research” (ISCR). The original Immunoscore® is a prognostic tool that categorizes the densities of CD3+ and CD8+ cells in both the invasive margin (IM) and center of the tumor (CT) in localized colon cancer, yielding a five-tiered classification (0–4). We evaluated the prognostic potential of ISCR and pathological complete response (pCR) following neoadjuvant chemotherapy (NACT). METHODS : The cohort included 53 TNBC, 32 luminal BC, and 18 HER2-positive BC patients undergoing NACT. Pre-treatment tumor biopsies were immune-stained for CD3+ and CD8+ T-cell markers. Quantitative analysis of these cells in different tumor locations was performed using computer-assisted image analysis. RESULTS : The pCR rate was 44%. Univariate analysis showed that primary tumor size, estrogen-receptor negative, progesteronereceptor negative, luminal vs. HER2-positive vs. TNBC, high Ki-67, high densities (cells/mm2 ) of CD3 CT, CD8+ CT, CD3+ IM, and CD8+ IM cells were associated with a high pCR. ISCR was associated with pCR following NACT. A multivariate model consisting of ISCR and the significant variables from the univariate analysis showed a significant trend for ISCR; however, the low sample size did not provide enough power for the model to be included in this study. CONCLUSIONS : These results revealed a significant prognostic role for the spatial distributions of the CD3+ , and CD8+ lymphocytes, as well as the ISCR in relation to pCR following NACT.Medical Oncology Centre of Rosebankhttps://www.mdpi.com/journal/cancersdm2022Immunolog

Predicting both passive intestinal absorption and the dissociation constant toward albumin using the PAMPA technique

The parallel artificial membrane permeability assay (PAMPA) is a high-throughput screening (HTS) method that is widely used to predict in vivo passive permeability through biological barriers, such as the skin, the blood brain barrier (BBB) and the gastrointestinal tract (GIT). The PAMPA technique has also been used to predict the dissociation constant (Kd) between a compound and human serum albumin (HSA) while disregarding passive permeability. Furthermore, the assay is based on the use of two separate 5-point kinetic experiments, which increases the analysis time. In the present study, we adapted the hexadecane membrane (HDM)-PAMPA assay to both predict passive gastrointestinal absorption via the permeability coefficient logPe value and determine the Kd. Two assays were performed: one in the presence and one in the absence of HSA in the acceptor compartment. In the absence of HSA, logPe values were determined after a 4-h incubation time, as originally described, but the dimethylsulfoxide (DMSO) percentage and pH were altered to be compatible with the protein. In parallel, a second PAMPA assay was performed in the presence of HSA during a 16-h incubation period. By adding HSA, a variation in the amount of compound crossing the membrane was observed compared to the permeability measured in the absence of HSA. The concentration of compound reaching the acceptor compartment in each case was used to determine both parameters (logPe and logKd) using numerical simulations, which highlighted the originality of this method because these calculations required only two endpoint measurements instead of a complete kinetic study. It should be noted that the amount of compound that reaches the acceptor compartment in the presence of HSA is modulated by complex dissociation in the receptor compartment. Only compounds that are moderately bound to albumin (-3<logKd [M]<-6) can be measured using this method. If compound permeability through the artificial membrane is low in the absence of HSA, the impact of complex formation/dissociation cannot be detected, and thus, logKd cannot be determined for this class of compounds. Thirteen compounds with known Kd values were analyzed using this method, and the obtained Kd values were in agreement with those obtained using primarily the gold-standard equilibrium dialysis. A linear correlation with a determination coefficient (r(2)) equal to 0.88 was obtained. This assay utilizes a technique that is currently routinely used in industrial companies to obtain permeability measurements; moreover, this approach is fast (96-well plate format), economical and easy to handle. This assay uses protein freely in solution, which may be more relevant than embedded proteins in chromatographic systems, for example. Finally, this method can be adapted to numerous other highly stable proteins

Reasons for grasslands to last in Western Brittany: an agrarian diagnosis

Reasons for grasslands to last in Western Brittany: an agrarian diagnosis. 26. General meeting of the European Grassland Federation (EGF) on The Multiple Roles of Grassland in the European Bioeconom

Tumor-Infiltrating Lymphocytes (TILs) in Early Breast Cancer Patients: High CD3+, CD8+, and Immunoscore Are Associated with a Pathological Complete Response

Background: Tumor-infiltrating lymphocytes are associated with a better prognosis in early triple-negative breast cancer (TNBC). These cells can be enumerated in situ by the &ldquo;Immunoscore Clinical Research&rdquo; (ISCR). The original Immunoscore&reg; is a prognostic tool that categorizes the densities of CD3+ and CD8+ cells in both the invasive margin (IM) and center of the tumor (CT) in localized colon cancer, yielding a five-tiered classification (0&ndash;4). We evaluated the prognostic potential of ISCR and pathological complete response (pCR) following neoadjuvant chemotherapy (NACT). Methods: The cohort included 53 TNBC, 32 luminal BC, and 18 HER2-positive BC patients undergoing NACT. Pre-treatment tumor biopsies were immune-stained for CD3+ and CD8+ T-cell markers. Quantitative analysis of these cells in different tumor locations was performed using computer-assisted image analysis. Results: The pCR rate was 44%. Univariate analysis showed that primary tumor size, estrogen-receptor negative, progesterone-receptor negative, luminal vs. HER2-positive vs. TNBC, high Ki-67, high densities (cells/mm2) of CD3 CT, CD8+ CT, CD3+ IM, and CD8+ IM cells were associated with a high pCR. ISCR was associated with pCR following NACT. A multivariate model consisting of ISCR and the significant variables from the univariate analysis showed a significant trend for ISCR; however, the low sample size did not provide enough power for the model to be included in this study. Conclusions: These results revealed a significant prognostic role for the spatial distributions of the CD3+, and CD8+ lymphocytes, as well as the ISCR in relation to pCR following NACT

The Immunoscore in Localized Urothelial Carcinoma Treated with Neoadjuvant Chemotherapy: Clinical Significance for Pathologic Responses and Overall Survival

International audience(1) Background-The five-year overall survival (OS) of muscle-invasive bladder cancer (MIBC) with neoadjuvant chemotherapy and cystectomy is around 50%. There is no validated biomarker to guide the treatment decision. We investigated whether the Immunoscore (IS) could predict the pathologic response to neoadjuvant chemotherapy and survival outcomes. (2) Methods-This retrospective study evaluated the IS in 117 patients treated using neoadjuvant chemotherapy for localized MIBC from six centers (France and Greece). Pre-treatment tumor samples were immunostained for CD3+ and CD8+ T cells and quantified to determine the IS. The results were associated with the response to neoadjuvant chemotherapy, time to recurrence (TTR), and OS. (3) Results-Low (IS-0), intermediate (IS-1-2), and high (IS-3-4) ISs were observed in 36.5, 43.7, and 19.8% of the cohort, respectively. IS was positively associated with a pathologic complete response (pCR; p-value = 0.0096). A high IS was found in 35.7% of patients with a pCR, whereas it was found in 11.3% of patients without a pCR. A low IS was observed in 48.4% of patients with no pCR and in 21.4% of patients with a pCR. Low-, intermediate-, and high-IS patients had five-year recurrence-free rates of 37.2%, 36.5%, and 72.6%, respectively. In the multivariable analysis, a high IS was associated with a prolonged TTR (high vs. low: p = 0.0134) and OS (high vs. low: p = 0.011). (4) Conclusions-This study showed the significant prognostic and predictive roles of IS regarding localized MIBC

Development and Validation of the QUALI-PALLI-FAM Questionnaire for Assessing Relatives' Perception of Quality of Inpatient Palliative Care: A Prospective Cross-Sectional Survey

International audienceContext: Relatives of patients receiving palliative care are at risk for psychological and physical distress, and their perception of quality of care can influence patients' quality of life. Objectives: The purpose of this study was to develop and validate the QUALI-PALLI-FAM questionnaire (QUAlity of PALLIative car from FAMilies' perspective) to measure families' perception of and satisfaction with palliative care. Methods: An exploratory factor analysis was conducted, and we evaluated the questionnaire's internal consistency using Cronbach's alpha, its stability across various strata, and the correlation between the QUALI-PALLI-FAM (factors, total score, and global satisfaction) and the total score of the FAMCARE (FAMily satisfaction with CARE) questionnaire. Results: This multicentric prospective cross-sectional survey was conducted in seven French hospitals, namely, three palliative care units and four standard medical units with a mobile palliative care team. The questionnaire was completed by 170 relatives of patients (more than 90% of patients had advanced cancer). The final questionnaire included 14 items across three domains: organization of care and availability of caregivers, medical information provision, and confidence and involvement of relatives. Internal consistency was good for all subscales (Cronbach's α = 0.74–0.86). Our questionnaire was stable across various strata: age and gender (patients and relatives), Palliative Performance Scale scores, and care settings. The QUALI-PALLI-FAM total score was correlated with the total FAMCARE score. Conclusion: The QUALI-PALLI-FAM appears to be a valid, reliable, and well-accepted tool to explore relatives' perception of quality of inpatient palliative care and complements the QUALI-PALLI-PAT questionnaire. Further testing is required in various settings and countries

Reverse Phenotyping in Patients with Skin Capillary Malformations and Mosaic GNAQ or GNA11 Mutations Defines a Clinical Spectrum with Genotype-Phenotype Correlation

International audienceNo abstract availabl

Low risk of embryonic and other cancers in PIK3CA ‐related overgrowth spectrum: Impact on screening recommendations

International audienceThe PIK3CA ‐related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%–21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long‐term follow‐up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples