GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Abstract A20: Analysis of tumor infiltrating lymphocytes and expression of PD1 and PD-L1 in breast tumors prior to and after neoadjuvant chemotherapy
    American Association for Cancer Research (AACR) ; 2018
    In:  Molecular Cancer Research Vol. 16, No. 8_Supplement ( 2018-08-01), p. A20-A20
    Details
    In: Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 16, No. 8_Supplement ( 2018-08-01), p. A20-A20
    Abstract: Introduction: The effect of chemotherapy on the presence of tumor-infiltrating lymphocytes (TILs) and expression of PD1 and PD-L1 is unclear. We sought to describe the differences in the percentage (%) of TILs, cytotoxic T lymphocytes (CTL), and expression of PD1/PD-L1 in tumors of patients (pts) with operable breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) who were enrolled in a biomarker study at our institution (IRB protocol# 2010C0036). Methods: A multicolor immune-histochemical multiplex assay simultaneously detecting PD1, PD-L1, and CD8 expressing cells was performed on formalin-fixed, paraffin-embedded diagnostic pretreatment biopsy or resected tumor specimen following NAC in 18 of 26 pts participating in the study. A cut-off of ≥1% was considered positive for PD1 and PD-L1 expression. We evaluated stromal and intratumoral CTLs by estimating % of stroma and tumor that contained CD8+ cells. In addition, stromal TILs (sTILs) were identified on full-face hematoxylin and eosin stained sections and defined as the % of tumor stroma containing infiltrating lymphocytes. Pathologic complete or near-complete response (pCR) was analyzed based on residual cancer burden (RCB) score and defined as RCB class 0 or I. Analysis of all slides was performed by an expert breast pathologist. Since the number of pts was limited, we only provide descriptive statistics (mean, range). In addition, because most pts had only a biopsy or only residual tumor available for the analysis, we divided pts into 2 separate cohorts based on what tissue was available. Results: Of 18 pts, biopsy was analyzed in 7 (Bx cohort) and residual tumor was analyzed in 11 pts (RT cohort). The median age of study pts was 48 (range 32-70); 11 (61%), 6 (33%), and 1 (6%) of pts were Caucasian, African American, and Hispanic, respectively. Ten pts (5 in Bx and RT cohorts each) had triple-negative BC (TNBC), 4 had HER2+ BC (1 and 3 in Bx and RT cohorts, respectively), and 4 had hormone receptor-positive, HER2- BC (1 and 3 in Bx and RT cohorts, respectively). Eight pts (44%) had pCR. In the bx cohort, 85% of pts had pCR while 18% of pts in the RT cohort had minimal residual disease (RCB class I). In the Bx cohort, average % of sTILs was 30% (range 2-70%), including 1 pt (14%) with lymphocyte predominant tumor (≥50% of sTILs). The % of sTILs was similar in the 11 residual tumors (mean 22, range 2-60) with 2 pts having lymphocyte predominant tumors. Average % of CTLs was 19 (range 1-50) in the Bx cohort and 14 (range 1-50) in the RT cohort. An average % of intratumoral CTLs was 8 (range 1-30) and 7.5 (range 0-40) while the average % of stromal CTLs was 25 (range 1-60) and 19 (range 1-60) in the Bx and RT cohorts, respectively. Similar % and trends were seen in 10 TNBC pts. PD-L1 expression was seen in 86% and 36% of tumors in the Bx and RT cohorts, respectively, with majority of expression present in the stroma. All cases of intratumoral PD-L1 expression were also positive for stromal PD-L1 expression. This difference was also seen in the TNBC pts (80% vs. 40% of tumors were PD-L1+ in Bx and RT cohorts, respectively). An average PD-L1 intensity was approximately 3% in both cohorts (range 1-20%). Expression of PD1 was very low (1% intensity in 3 pts in Bx cohort and in 1 pt in RT cohort) and it was seen on CD8+ CTLs. Conclusion: Our study preliminarily shows that percent of sTILs and stromal and intratumoral CTLs does not differ between pretreatment biopsy and residual tumors following NAC. Lower proportion of residual tumors were PD-L1+ compared to pretreatment biopsy specimen. The study limitations include small number of subjects and lack of comparison in the same pts. Future studies are needed to confirm these findings. Citation Format: Robert Wesolowski, Zaibo Li, Christopher McQuinn, Maryam Lustberg, Bhuvaneswari Ramaswamy, Anne Noonan, Raquel Reinbolt, Sagar Sardesai, Jeffrey B. VanDeusen, Nicole Williams, William E. Carson, III. Analysis of tumor infiltrating lymphocytes and expression of PD1 and PD-L1 in breast tumors prior to and after neoadjuvant chemotherapy [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A20.
    Type of Medium: Online Resource
    ISSN: 1541-7786 , 1557-3125
    URL: Article
    DOI: 10.1158/1557-3125.ADVBC17-A20
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2097884-4
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Exploratory analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients receiving neo-adjuvant chemotherapy for operable breast cancer
    Springer Science and Business Media LLC ; 2020
    In:  BMC Cancer Vol. 20, No. 1 ( 2020-12)
    Details
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: While combinations of immune checkpoint (ICP) inhibitors and neo-adjuvant chemotherapy (NAC) have begun testing in patients with breast cancer (BC), the effects of chemotherapy on ICP expression in circulating T cells and within the tumor microenvironment are still unclear. This information could help with the design of future clinical trials by permitting the selection of the most appropriate ICP inhibitors for incorporation into NAC. Methods Peripheral blood samples and/or tumor specimens before and after NAC were obtained from 24 women with operable BC. The expression of CTLA4, PD-1, Lag3, OX40, and Tim3 on circulating T lymphocytes before and at the end of NAC were measured using flow cytometry. Furthermore, using multi-color immunohistochemistry (IHC), the expression of immune checkpoint molecules by stromal tumor-infiltrating lymphocytes (TILs), CD8+ T cells, and tumor cells was determined before and after NAC. Differences in the percentage of CD4+ and CD8+ T cells expressing various checkpoint receptors were determined by a paired Student’s t-test. Results This analysis showed decreased ICP expression by circulating CD4+ T cells after NAC, including significant decreases in CTLA4, Lag3, OX40, and PD-1 (all p values 〈  0.01). In comparison, circulating CD8+ T cells showed a significant increase in CTLA4, Lag3, and OX40 (all p values 〈  0.01). Within tumor samples, TILs, CD8+ T cells, and PD-L1/PD-1 expression decreased after NAC. Additionally, fewer tumor specimens were considered to be PD-L1/PD-1 positive post-NAC as compared to pre-NAC biopsy samples using a cutoff of 1% expression. Conclusions This work revealed that NAC treatment can substantially downregulate CD4+ and upregulate CD8+ T cell ICP expression as well as deplete the amount of TILs and CD8+ T cells found in breast tumor samples. These findings provide a starting point to study the biological significance of these changes in BC patients. Trial registration NCT04022616 .
    Type of Medium: Online Resource
    ISSN: 1471-2407
    URL: Article
    DOI: 10.1186/s12885-020-06949-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041352-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Abstract 5514: Analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients pre- and post-neoadjuvant chemotherapy for operable breast cancer
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5514-5514
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5514-5514
    Abstract: While combinations of immune checkpoint (ICP) inhibitors and neo-adjuvant chemotherapy (NAC) have begun to be tested in patients with breast cancer (BC), chemotherapeutic effects on ICP expression in circulating T cells are still unclear. This information could help design future clinical trials including the selection of the best ICP inhibitors to be incorporated into NAC and finding predictive/prognostic biomarkers. Peripheral blood samples and/or tumor specimens before and after NAC were obtained from twenty-four women with operable BC. Using flow cytometry, the expression of CTLA4, PD-1, Lag3, OX40, and Tim3 on circulating T lymphocytes before and at the end of NAC were measured. Differences in the percentage of CD4+ and CD8+ T cells expressing various checkpoint receptors pre- and post-NAC were determined by a paired t-test. This data showed decreased ICP expression after NAC by circulating CD4+ T cells, including significant decreases in CTLA4 (p & lt;0.001), Lag3 (p & lt;0.001), OX40 (p & lt;0.001), and PD-1 (p & lt;0.001). In comparison, circulating CD8+ T cells showed a significant increase in CTLA4 (p & lt;0.003), Lag3 (p=0.001), and OX40 (p & lt;0.001). In comparing breast cancer subtypes, it was found there were significantly lower amounts of circulating Lag3+ CD4+ T cells from triple-negative (lacking estrogen, progesterone, and HER2 receptor expression) breast cancer patients than those from breast cancer patients with tumors expressing at least one of these receptors. Furthermore, using multi-color immunohistochemistry (IHC), the expression of stromal tumor infiltrating lymphocytes (TILs), CD8+ T cells, and PD-1/PD-L1 within the tumor were determined before and after NAC. This analysis revealed fewer tumor specimens were considered to be PD-L1/PD-1 positive post-NAC as compared to pre-NAC biopsy samples using a cutoff of 1% or greater expression. Overall, this work reveals that NAC has opposing effects on ICP expression by CD4+ and CD8+ T cells as well as provides a starting point to study the biological significance of these changes in BC patients.Trial registration: NCT04022616 Citation Format: Dionisia M. Quiroga, Andrew Stiff, Christopher McQuinn, Zaibo Li, Hiroaki Nitta, Himanshu Savardekar, Brooke Benner, Bhuvaneswari Ramaswamy, Maryam Lustberg, Rachel Layman, Erin Macrae, Mahmoud Kassem, Nicole Williams, Sagar Sardesai, Jeffrey VanDeusen, Daniel Stover, Mathew Cherian, Thomas Mace, Lianbo Yu, Megan Duggan, William E. Carson, Robert Wesolowski. Analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients pre- and post-neoadjuvant chemotherapy for operable breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for C ancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5514.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-5514
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Effect of neoadjuvant chemotherapy on immune checkpoint expression in breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e12126-e12126
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e12126-e12126
    Abstract: e12126 Background: Even with neo-adjuvant chemotherapy (NAC) many breast cancer (BC) patients (pts) relapse, especially triple negative pts. The incorporation of checkpoint inhibitors into NAC for BC is being tested in clinical trials. How NAC affects checkpoint receptor expression is not known. Such information could aid in the rational selection of checkpoints to target during NAC. We sought to characterize changes in the frequency of circulating CD4 and CD8 T cells expressing PD1, CTLA4, LAG3, TIM3, and OX40 over the course of NAC. Methods: In this prospective trial, expression of PD-1, CTLA-4, Lag3, Tim3 and Ox40 on circulating CD4 and CD8 T cells were measured by FACS analysis in pts with operable breast cancer (BC) prior and at the end of NAC. The primary objective was to explore the association between NAC and expression levels of the immune checkpoints. Results: 1, 20 and 3 pts had clinical stage I, II, IIIA, respectively. Median age was 48. 11, 6 and 7 pts were triple negative (TN), HER2+ and hormone receptor (HR)+, respectively. Complete pathologic response rate was 45.8%. Globally CD4 T cells expressing CTLA4, Lag3, Ox40 and PD1 decreased following NAC (all p 〈 0.01). Conversely, CD8 T cells expressing CTLA4, Lag3 and Ox40 significantly increased (all p 〈 0.01). More CD8 T cells from HER2+ pts expressed Lag3 prior to therapy compared to HR+ pts (p 〈 0.05) with a similar trend compared to TN pts. Prior to therapy more CD8 T cells from HER2+ and TN pts expressed Tim3 compared to HR+ pts (p 〈 0.05 for each). Post therapy more CD4 T cells from HER2+ pts expressed PD1 compared to HR+ and TN pts (p = 0.027 and 0.018 respectively). Clinical response did not predict change in checkpoint expression. An interaction analysis revealed that HER2+ disease predicted a drop in CTLA4 CD4 T cells and a drop in Lag3 CD4 and CD8 T cells over NAC (p 〈 0.05). Conclusions: This analysis identified changes in checkpoint receptor expression by CD4 and CD8 T cells in BC pts after NAC. Differences in checkpoint receptor expression were found between BC subgroups. This data provides a starting point for understanding checkpoint receptor expression changes with NAC, and could help guide the selection and timing of incorporating checkpoint inhibitors in BC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e12126
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...