About

Anushka Dongre, PhD, is an Assistant Professor in the Department of Biomedical Sciences and an Adjunct Assistant Professor in the Department of Microbiology and Immunology. She completed her graduate studies at the University of Massachusetts-Amherst under Dr. Barbara A. Osborne, where she demonstrated the importance of Notch signaling in regulating T-cell function. Following this, she pursued postdoctoral training with Dr. Robert A. Weinberg at the Whitehead Institute for Biomedical Research, MIT. During her postdoctoral work, she showed that the epithelial-mesenchymal transition contributes to the establishment of an immunosuppressive tumor microenvironment and drives resistance of breast cancers to immune checkpoint blockade therapy. Dr. Dongre chairs the executive committee of the Cancer Metabolism Focus Group (CMFG) at Cornell and serves on the communications sub-committee of the AACR-Cancer Immunology Working Group. Her research interests lie at the intersection of cancer biology and immunology, with a particular focus on understanding mechanisms that regulate tumor microenvironments and immune responses. She is also passionate about mentoring the next generation of graduate and undergraduate students. Outside of her professional work, she enjoys painting, playing the piano, and spending time with her family and her dog, Wilkie.

Research topics

• Medicine
• Biology
• Immunology
• Cancer research
• Cell biology
• Internal medicine
• Oncology

Selected publications

• The role of naturally-occurring canine tumors in translating conserved consequences of epithelial-mesenchymal plasticity to human cancers

  Frontiers in Veterinary Science · 2026-04-20

  articleOpen accessSenior author

  Epithelial-mesenchymal plasticity (EMP) is a dynamic cellular process that confers motility to epithelial cells. In carcinomas, this program advances disease progression by promoting therapy resistance, recurrent disease, and spread to distant organ sites. The mechanisms of these clinical consequences are well studied in mouse models. However, mouse models lack physiologically relevant features of human cancers, including tumor heterogeneity, immune experience, and common environmental exposures. To address this, many groups have turned to naturally-occurring cancers in companion animals. This approach, known as comparative oncology, provides a model with conserved molecular mechanisms, similar environmental and immunological exposures, and realistic tumor heterogeneity. Moreover, companion animals receive the same treatment modalities as human patients and clinical trials can be executed with reduced cost and often in a shorter time frame. Therefore, studying EMP in companion animals, such as dogs, can help identify conserved features and therapeutic vulnerabilities. Here, we review consequences of EMP in four canine cancers: mammary, prostate, squamous cell, and urothelial carcinoma, with a focus on conserved features between murine models and disease in canine and human patients.

  PublisherDOI

• Abstract 2800: Understanding the mechanism by which CD4+ T cells sensitize mesenchymal CD73-deficient tumors to anti-CTLA4 immune checkpoint blockade therapy

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Triple-Negative Breast Cancer (TNBC) is a highly aggressive disease with poor patient outcomes due to its resistance to chemotherapy and immunotherapy. Despite its efficacy in Melanoma and Lung carcinoma, immune checkpoint blockade (ICB) therapy is only effective in a small minority of TNBC patients. Epithelial-to-Mesenchymal Transition (EMT) is a key driver of malignant progression leading to greater metastatic potential and an immunosuppressive tumor microenvironment, driving resistance to therapies. Our previous results demonstrate that epithelial tumors respond to anti-CTLA4 therapy while mesenchymal tumors are resistant. Strikingly, knockout of CD73 in mesenchymal tumors results in complete sensitization to anti-CTLA4 treatment but not anti-PD1 therapy, the more clinically used treatment. Using our preclinical mouse models together with immunofluorescence staining, we observed that CD73-deficient tumors display increased infiltration of CD4+ and CD8+ T cells upon anti-CTLA4 treatment relative to non-responding controls. Most notably, while CD73 deficient tumors continued to respond to anti-CTLA4 treatment without CD8+ T cells, they failed to respond in the absence of CD4+ T cells. However, the mechanisms by which CD4+ T cells facilitate the elimination of mesenchymal tumors remain unknown. Preliminary results demonstrate that cytotoxic CD4+ T cells play a crucial role in potentiating the response of CD73-deficient tumors to anti-CTLA4. Moreover, tumors contain plastic CD4+ T cell subsets that reduce immune suppression under anti-CTLA4 treatment while promoting immune suppression under anti-PD1 treatment. These results reveal that CD4+ T cells can specifically target lethal mesenchymal cancer cells in response to anti-CTLA4 but not anti-PD1 therapy. Future work is aimed at understanding whether CD4+ T cells eliminate tumors via direct interactions with cancer cells or through indirect activation of other immune cells. Given the inefficacy of anti-PD1 therapy in TNBC clinical trials, characterizing the CD4+ T cell response to anti-CTLA4 provides a mechanistic basis for leveraging its therapeutic potential. Citation Format: Brian Hongtao Feng, Caitie Hanna Sams, Isabel O'Connell, Shiney Chandraganti, Anushka Dongre, . Understanding the mechanism by which CD4+ T cells sensitize mesenchymal CD73-deficient tumors to anti-CTLA4 immune checkpoint blockade therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2800.

  PublisherDOI

• Epithelial-mesenchymal plasticity and immunosuppression in canine carcinomas reveals cross-species upregulation of CD109

  Communications Biology · 2026-01-22 · 1 citations

  articleOpen accessSenior authorCorresponding

  Epithelial-mesenchymal plasticity (EMP) is activated in carcinoma cells to drive metastasis and chemoresistance. Recently, we demonstrated that EMP activation results in an immunosuppressive tumor microenvironment and immunotherapy resistance in a syngeneic orthotopic murine model. However, it has yet to be shown whether this is conserved in canine carcinomas. Here, we show that in spontaneous canine mammary carcinomas (CMCs), which share clinical and molecular features with human breast cancers, EMP is linked to the recruitment of immunosuppressive cells. Additionally, we identify that the glycoprotein CD109 is associated with EMP-mediated immunosuppression in canine, murine, and human models. CD109 has been associated with tumorigenicity, but not immunosuppression in cancers of any species. Finally, we identified shared upregulation of immunosuppressive factors across multiple canine carcinomas, including oral squamous cell carcinoma, urothelial carcinoma, and pulmonary carcinoma. These findings demonstrate that EMP is associated with immunosuppression in canine carcinomas, with translational implications for human breast cancers.

  PublisherOA PDFDOI

• Abstract 7392: A cancer cell-intrinsic PAR1/MALT1/PD-L1 signaling pathway drives immune evasion in triple-negative breast cancer

  Cancer Research · 2026-04-03

  article

  Abstract Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and remains difficult to treat due to the absence of targeted therapies. While recent advances in immunotherapy, particularly with immune checkpoint inhibitors (ICIs), have transformed the treatment landscape for many cancers, response rates to ICIs remain low for TNBC, largely due to tumor-intrinsic immune evasion mechanisms. Objective: We identify and characterize a novel immune evasion pathway in TNBC driven by deregulation of cancer cell-intrinsic protease-activated receptor 1 (PAR1), a thrombin receptor frequently upregulated in aggressive tumors. Methods and Results: Through integrative bioinformatic analyses, genetic perturbations, xenograft models (immunodeficient and immunocompetent), flow cytometry-based tumor immune profiling, and RNA-seq, we demonstrate that PAR1 activation enhances immune evasion in TNBC. Mechanistically, we show that the paracaspase MALT1 acts as a critical downstream effector of PAR1 signaling and promotes immune escape by driving PD-L1 expression in TNBC cells. Functional assays reveal that genetic depletion of MALT1 or PD-L1 increases TNBC cell susceptibility to T cell-mediated cytotoxicity in vitro and significantly suppresses tumor growth in vivo. Notably, through knock-in and rescue experiments using a catalytically inactive MALT1 mutant, we reveal that MALT1’s scaffolding - rather than protease - function is essential for PD-L1 regulation. Immune cell depletion assays further identify CD4+ T cells, CD8+ T cells, and natural killer (NK) cells as key mediators of the anti-tumor immune response suppressed by the PAR1-MALT1 axis. These findings are supported by human TNBC specimen analyses, where MALT1 expression inversely correlates with T cell activation and positively associates with PD-L1 in PAR1-high, but not PAR1-low, tumors. Conclusion: Our study reveals immune evasion as a novel mechanism of PAR1-driven breast cancer pathogenesis, mediated by a PAR1/MALT1/PD-L1 signaling cascade. These findings bridge a critical gap by positioning MALT1 at the interface between tumor-intrinsic signaling and the immune microenvironment - two areas of CARMA-BCL10-MALT1 (CBM) complex research that have largely evolved in parallel over the years. Importantly, targeting MALT1 may enhance immunotherapy efficacy in TNBC. Given the availability of MALT1 inhibitors in clinical development, our work supports combining MALT1 inhibition with ICIs or other immune-oncology agents as a promising strategy to overcome immune resistance in TNBC. Citation Format: Dong Hu, Prasanna Ekambaram, Zheqi Li, Linda Klei, Maria L. Beecher, Yi Liu, Zongyou Cai, John Little, Jeffrey A. Meridew, Jia-Ying Lee, E. Aubrey Thompson, Tullia C. Bruno, Lidija Covic, Seung-Oe Lim, Anushka Dongre, Heide L. Ford, Mien-Chie Hung, Adrian V. Lee, Steffi Oesterreich, Linda McAllister-Lucas, Peter C. Lucas. A cancer cell-intrinsic PAR1/MALT1/PD-L1 signaling pathway drives immune evasion in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7392.

  PublisherDOI

• CD4 ⁺ T-cells sensitize quasi-mesenchymal breast tumors lacking CD73 to anti-CTLA4 immune checkpoint blockade therapy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-13 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Although immune checkpoint blockade therapy has generated dramatic responses in certain cancer types, breast tumors are largely unresponsive. Epithelial-mesenchymal plasticity leads to the assembly of an immunosuppressive tumor microenvironment and drives resistance of breast tumors to immunotherapies. Importantly, targeting CD73 completely sensitizes quasi-mesenchymal breast tumors to anti-CTLA4 immune checkpoint blockade therapy. However, the mechanism(s) of sensitization remained unknown. We demonstrate that targeting CD73 in quasi-mesenchymal breast tumors sensitizes them to anti-CTLA4 immune checkpoint blockade therapy in a CD4+ T-cell dependent manner. Moreover, epithelial-mesenchymal plasticity results in elevated expression of cancer cell-intrinsic CD73 in human triple negative breast cancers. Given the ability of quasi-mesenchymal cancer cells to metastasize and resist multiple therapies, these findings can instruct the formation of translational strategies for the treatment of human breast cancers. These findings also bring to the forefront the attractive possibility of utilizing the phenotypic plasticity of cancer cells along with CD73 and CD4+ T-cells as a predictive criterion for immunotherapy responsiveness.

  PublisherOA PDFDOI

• p95HER2, a truncated form of the HER2 oncoprotein, drives an immunosuppressive program in HER2+ breast cancer that limits trastuzumab deruxtecan efficacy

  Nature Cancer · 2025-06-27 · 7 citations

  article
  PublisherDOI

• Women in STEM becoming independent: Asking for help creates opportunities for connections and kindness

  The Journal of Experimental Medicine · 2025-09-17

  articleOpen access

  This year at JEM, we are highlighting women in science by sharing their stories and amplifying their voices. In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher.

  PublisherOA PDFDOI

• Epithelial-Mesenchymal Plasticity is Associated with Immunosuppressive Features in Canine Mammary Carcinomas

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-21

  preprintOpen accessSenior authorCorresponding

  Abstract Epithelial-mesenchymal plasticity (EMP) is a cellular process activated in carcinoma cells to drive invasiveness, metastasis, and chemoresistance. Recently, we have demonstrated that activation of the EMP program also results in the assembly of an immunosuppressive tumor microenvironment and resistance to immunotherapy in an immunocompetent orthotopic murine model. However, it has yet to be shown whether these findings can be translated to canine carcinomas. Here, we show that in spontaneous canine mammary carcinomas (CMCs), which share similar histopathologic, molecular, and clinical features with human breast cancers, EMP activation is linked to the recruitment of immunosuppressive cells including regulatory T-cells and M2-like macrophages. Additionally, through transcriptomic profiling of CMCs, we identify that the glycoprotein CD109 is associated with EMP-mediated immunosuppression across canine, murine, and human breast cancer models. CD109 has been previously associated with tumorigenicity, but not immunosuppression in cancers of any species. Finally, we identified upregulation of several immunosuppressive paracrine factors across multiple canine carcinomas, including oral squamous cell carcinoma, urothelial carcinoma, and pulmonary carcinoma samples. These findings demonstrate for the first time that the EMP program is associated with immunosuppression in canine carcinomas, with direct translational implications for human breast cancers.

  PublisherDOI

• Abstract B022: Targeting epithelial-mesenchymal plasticity and CD73 to enhance responses of breast cancers to immune checkpoint blockade therapies

  Cancer Research · 2024-02-01

  article1st authorCorresponding

  Abstract Immune checkpoint blockade (ICB) therapy has generated dramatic responses in certain types of human tumors however, the response of breast cancers has been largely limited. Epithelial-mesenchymal plasticity (EMP) enables carcinoma cells to metastasize, gain tumor-initiating ability and mount resistance to chemotherapies. In addition, we have demonstrated that this plasticity program also contributes to the establishment of an immunosuppressive tumor microenvironment and confers resistance to ICB therapy (Dongre and Weinberg 2019). By establishing novel, preclinical models of more-epithelial or more-mesenchymal breast tumors, we observed that epithelial tumors recruit CD8+ T-cells to their microenvironment and are sensitive to anti-CTLA4 ICB. In contrast, mesenchymal tumors recruit Tregs and M2-like macrophages and are resistant to the same treatment (Dongre et al., 2017). Strikingly, abrogation of CD73 from more-mesenchymal cells completely sensitizes otherwise refractory tumors to anti-CTLA4 ICB (Dongre et al., 2021). These findings demonstrated for the first time that more-mesenchymal breast cancer cells can be completely sensitized to anti-tumor immunity by interrupting certain cell-intrinsic signaling channels. However, the underlying mechanisms of such sensitization remain elusive. Additionally, the regulatory networks that control the expression of CD73 itself in more-mesenchymal but not epithelial breast cancer cells are not well defined. To determine the subset of T-cells that is functionally important in sensitizing mesenchymal tumors lacking CD73, we depleted either conventional CD4+ T-cells or CD8+ cytotoxic T-cells in combinatoin with ICB. While responding mice recruited both T-cells to their tumors, only CD4+ T-cells (and not CD8+ T-cells) were functionally important in driving sensitization. Along these lines, more-mesenchymal cancer cells lacking CD73 failed to respond to anti-CTLA4 ICB when propagated in genetically engineered mice lacking CD4+ T-cells relative to wild type controls. Importantly, depletion of CD4+ T-cells also prevented the recruitment of peripheral CD8+ T-cells to responding tumors, thereby driving resistance to ICB. In addition, we observed that human triple negative breast cancer cell lines expressed the highest amount of CD73 relative to hormone receptor-positive cell lines. Most importantly, activating EMP in human breast cancer cells by doxycycline-controlled expression of various transcription factors, induced the expression of CD73. Taken together, our work demonstrates that (i) the phenotypic plasticity of breast cancer cells can predict responses to ICB (ii) targeting CD73 can completely sensitize more-mesenchymal tumors to anti-CTLA4 ICB in a CD4+ T-cell dependent fashion and; (iii) altering the cellular plasticity of cancer cells can regulate CD73 expression. Given the highly refractory nature of more-mesenchymal cancer cells, our findings hold tremendous potential in aiding translational efforts to target cancer plasticity to enhance responses of breast cancers to ICB therapy. Citation Format: Anushka Dongre. Targeting epithelial-mesenchymal plasticity and CD73 to enhance responses of breast cancers to immune checkpoint blockade therapies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B022.

  PublisherDOI

• Abstract 6556: Targeting mesenchymal tumor cell-intrinsic factors sensitizes refractory tumors to immune checkpoint blockade therapy

  Cancer Research · 2024-03-22

  articleSenior author

  Abstract Immune checkpoint blockade (ICB) therapy has emerged as a promising approach for treating breast cancer, however, only a fraction of patients derives clinical benefit and the underlying reasons for heterogeneous responses remain elusive. The epithelial-to-mesenchymal transition (EMT) enables these carcinomas to metastasize and acquire resistance to chemotherapy. We have recently demonstrated that the EMT program also confers resistance to immunotherapies. Specifically, epithelial tumors recruit CD8+ T-cells to the tumor microenvironment and are sensitive to anti-CTLA4 ICB. In contrast, mesenchymal tumors assemble an immunosuppressive tumor microenvironment and are resistant to the same treatment. Furthermore, mesenchymal tumors express multiple immunosuppressive paracrine factors relative to their epithelial counterparts. Of these, abrogation of CSF1 or SPP1 from mesenchymal cancer cells generates partial responses to ICB therapy. Strikingly, abrogation of CD73 from mesenchymal carcinoma cells completely sensitizes otherwise refractory tumors to immunotherapy. While targeting cancer cell-intrinsic factors can sensitize mesenchymal tumors to ICB, the mechanisms that dictate partial versus complete responses are unclear. Furthermore, whether abrogation of CD73 can also sensitize mesenchymal tumors to other forms of ICB remains unknown. By performing immunofluorescent analysis of tumor sections, we observed that knockout of CD73 promoted the greatest infiltration of both CD4+ and CD8+ T-cells in response to anti-CTLA4 ICB compared to tumors knocked out for CSF1 and SPP1, which showed only intermediate levels of infiltration. Moreover, treatment of mesenchymal tumor-bearing mice with anti-CD73 generated synergistic responses with anti-CTLA4 ICB, but not with anti-PD1, or combinations of anti-CTLA4 and anti-PD1. In conclusion, our results demonstrate that the EMT program in cancer cells is predictive of responses to ICB. Targeting CD73 in mesenchymal breast tumors promotes an influx of both CD4+ and CD8+ T-cells and potentiates the efficacy of anti-CTLA4 ICB. Through mining of canine mammary tumor RNA sequencing data, we have found that canine tumors associated with EMT have increased expression of CD73, which suggests that these mechanisms of immune evasion may translate across species. These findings could promote therapies for both animals and humans that sensitize highly refractory populations of more-mesenchymal cancer cells. Citation Format: Kimaya M. Bakhle, Caitie H. Sams, Anushka Dongre. Targeting mesenchymal tumor cell-intrinsic factors sensitizes refractory tumors to immune checkpoint blockade therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6556.

  PublisherDOI

Frequent coauthors

• Robert A. Weinberg

  Whitehead Institute for Biomedical Research

  67 shared

• Ferenc Reinhardt

  Whitehead Institute for Biomedical Research

  49 shared

• Zuzana Keckesova

  Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

  39 shared

• Mohammad Rashidian

  Dana-Farber Cancer Institute

  37 shared

• Hidde L. Ploegh

  Boston Children's Museum

  33 shared

• Aaron Bagnato

  22 shared

• Jasmine M. De Cock

  12 shared

• Anna Martner

  11 shared

Labs

• Dongre LabPI

Education

• PhD, Osborne Lab

  University of Massachusetts

Awards & honors

• Byron Prize for outstanding PhD dissertation
• Ludwig Cancer Research Postdoctoral Fellowship
• Whitehead Institute Postdoc Association Education Award
• Keystone Symposia Future of Science Fund Scholarship
• AACR Scholar-In-Training Award