Dataset Information

Dissimilar patterns of tumor-infiltrating immune cells at the invasive tumor front and tumor center are associated with response to neoadjuvant chemotherapy in primary breast cancer.

ABSTRACT: BACKGROUND:Tumor-infiltrating lymphocytes (TILs) are described as an important immune modulator in the tumor microenvironment and are associated with breast cancer (BC) outcome. The spatial analysis of TILs and TIL subtype distribution at the invasive tumor front (ITF) and the tumor center (TC) might provide further insights into tumor progression. METHODS:We analyzed core biopsies from 87 pre-therapeutic BC patients for total TILs and the following subtypes: CD3+, CD4+, CD8+, CD20+ and CD68+ cells in correlation to clinicopathological parameters and disseminated tumor cells (DTCs) in the bone marrow. RESULTS:TILs and TIL subtypes showed significantly different spatial distribution among both tumor areas. TILs, especially CD3+ T cells were associated with the tumor status and tumor grading. BC patients responding to neoadjuvant chemotherapy had significantly more TILs and CD3+ T cells at the TC. The presence of DTCs after NACT was related to CD4+ infiltration at the TC. CONCLUSION:The dissimilar spatial association of TILs and TIL subtypes with clinicopathological parameters, NACT response and minimal residual disease underlines the necessity of detailed TIL analysis for a better understanding of immune modulatory processes.

SUBMITTER: Konig L

PROVIDER: S-EPMC6360695 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Dissimilar patterns of tumor-infiltrating immune cells at the invasive tumor front and tumor center are associated with response to neoadjuvant chemotherapy in primary breast cancer.

König Lisa L Mairinger Fabian D FD Hoffmann Oliver O Bittner Ann-Kathrin AK Schmid Kurt W KW Kimmig Rainer R Kasimir-Bauer Sabine S Bankfalvi Agnes A

BMC cancer 20190204 1

<h4>Background</h4>Tumor-infiltrating lymphocytes (TILs) are described as an important immune modulator in the tumor microenvironment and are associated with breast cancer (BC) outcome. The spatial analysis of TILs and TIL subtype distribution at the invasive tumor front (ITF) and the tumor center (TC) might provide further insights into tumor progression.<h4>Methods</h4>We analyzed core biopsies from 87 pre-therapeutic BC patients for total TILs and the following subtypes: CD3+, CD4+, CD8+, CD2 ...[more]

PMID: 30717704

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Project description:PurposeThis study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated.MethodsThis retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change. Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed.ResultsOf the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group.ConclusionOur study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI.Trial registrationClinicalTrials.gov Identifier: NCT04909554.

Project description:BACKGROUND:Regulatory T cells(Tregs) and myeloid-derived suppressor cells(MDSCs) represent two immunosuppressive cell populations that are important in the establishment and maintenance of cancer immune tolerance. MDSCs can express IDO and promote immune tolerance via expansion of Treg cell. METHOD:We use needle biopsy breast cancer tissues prior to neoadjuvant chemotherapy(NCT) staining for CD33, Foxp3 and IDO by immunohistochemistry to evaluate whether they were correlated with subsequent treatment responses in breast cancer. RESULTS:Expressions of IDO, CD33+MDSCs and Foxp3+Tregs were correlated with each other. Immunohistochemical double staining revealed that IDO expression in CD33+MDSCs was positively correlated with Foxp3+Tregs (P < 0.05). CD33+MDSCs, Foxp3+Tregs, and IDO expression in tumor tissues were associated with advanced clinical stage prior to NCT (P < 0.05). CD33+MDSCs, Foxp3+Tregs, IDO expression, IDO expression in CD33+MDSCs and clinical T3-T4 stage prior to NCT, pathological T3-T4 stage, ER(+), luminal type were correlated with clinical responses of PD+SD (P < 0.05). Multivariate analysis showed that CD33+MDSCs, IDO expression, IDO expression in CD33+MDSCs, and advanced pathological T stage were risk factors for PD+SD. Focusing on the pCR of NCT, only CD33+MDSCs, clinical T3-T4, and N1-N3 stage prior to NCT were associated with no-pCR (P < 0.05). The multivariate analysis showed that advanced clinical T stage and N stage were risk factors for no-pCR. Clinical stage prior to NCT were significantly correlated with progression free survival (P = 0.021), while Foxp3+Tregs and clinical T stage were significantly correlated with overall survival (P = 0.022 and P = 0.001, respectively). Foxp3+Treg was significant risk factor for overall survival after adjusting covariates by COX regression. CONCLUSION:Tumor-infiltrating MDSCs, Tregs, IDO expression and IDO expression in MDSCs were correlated with clinicopathological features, NCT response, and prognosis of breast cancer patients, suggesting that they might be potential markers for clinical outcomes of NCT and help clinical decision-making for improved therapies for breast cancer.

Project description:BackgroundNeoadjuvant chemotherapy is underutilized in bladder cancer patients who undergo radical cystectomy. However, the quality of regimens used in this setting remains largely unknown.ObjectiveTo determine utilization treatment patterns and survival outcomes according to regimens administered.Design, setting, and patientsWe used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database to identify patients diagnosed with clinical stage TII-IV bladder cancer from January 1, 2001 to December 31, 2011.Outcome measurements and statistical analysisTemporal trends were assessed using the Cochran-Armitage test. Multivariable logistic regression models were used to identify predictors for neoadjuvant chemotherapy use. Cox proportional hazards models were used to compare overall survival according to regimens administered.Results and limitationsOf 2738 patients treated with radical cystectomy, 344 (12.6%) received neoadjuvant chemotherapy. The agents most commonly used were gemcitabine (72.3%), cisplatin (55.2%), and carboplatin (31.1%). The regimens most commonly used were gemcitabine-cisplatin (45.3%), gemcitabine-carboplatin (24.1%), and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC; 6.7%). Use of neoadjuvant chemotherapy more than tripled during the study period, from 5.7% in 2001 to 17.3% in 2011 (p<0.001). The quality of the regimen administered impacted survival outcomes, as M-VAC use was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer (hazard ratio 0.24, 95% confidence interval 0.07-0.86; p=0.030]. Limitations include the limited ability of retrospective analysis to control for selection bias.ConclusionsNeoadjuvant chemotherapy was underused, and the quality of neoadjuvant chemotherapy regimens administered for bladder cancer was inconsistent with guideline recommendations. These findings are important when interpreting population-based data on the use of chemotherapy and extrapolating survival outcomes.Patient summaryIn a large population-based study, 12.6% of patients undergoing radical cystectomy for bladder cancer received neoadjuvant chemotherapy, half of whom received guideline-recommended regimens. The quality of the regimen impacted survival outcomes, as use of cisplatin-based chemotherapy was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer. However, <1% of radical cystectomy patients received this regimen.

Dataset Information

Dissimilar patterns of tumor-infiltrating immune cells at the invasive tumor front and tumor center are associated with response to neoadjuvant chemotherapy in primary breast cancer.

Publications

Dissimilar patterns of tumor-infiltrating immune cells at the invasive tumor front and tumor center are associated with response to neoadjuvant chemotherapy in primary breast cancer.

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