CODEX analysis of the immune microenvironment in human triple-negative breast cancer

Cancer Immunology Program

Mission Statement:

To foster immunology-focused research and build community centered on the investigation of unmet needs in the cancer field including early-onset cancers and immune-resistant cancers.

 

Overview:

Immunology has transformed cancer treatment over the last decade. Building on the initial successes of high-dose IL-2, administration of tumor-infiltrating lymphocytes (TIL), and vaccination, the 2011 FDA approval of Ipilimumab, an antibody that blocks the immune checkpoint receptor CTLA4, for the treatment of advanced melanoma initiated a new era in the field of Immuno-Oncology. The development of immune checkpoint inhibitors (ICIs) as a class of biologic drugs ensued. Currently, anti-PD1, anti-PD-L1, and anti-LAG-3 are approved, either singly or in combination, for different solid tumor indications. Alongside the development of ICIs, the generation of engineered T cells, exemplified by chimeric antigen receptor (CAR) T cells, showed great success in the treatment of liquid tumors, specifically B cell malignancies. Accordingly, in 2013, Cancer Immunotherapy was named as the Breakthrough of the Year by Science. In 2018, James P. Allison and Tasuko Honjo, two eminent immunologists who paved the way for the development of ICI therapies, were awarded the Nobel Prize in Physiology and Medicine.

Despite the remarkable success of ICIs and engineered T cell therapies, many cancer patients still do not benefit from these advancements, and the incidence of some cancers is increasing at alarming rates in younger individuals (<50 years of age). Although the underlying reasons for these observations are likely complex, one reason may lie in the tumor tissue itself. The tumor microenvironment (TME) is complex, heterogenous, and variable across tumors, metastases, and tumor types. The advent of technologies that allow for the visualization of immune cells and their associated proteomes and transcriptomes in tissue provide a critical tool for gaining insight into tissue-driven cues that determine resistance to immune-based therapies and, possibly, accelerated onset of cancer in younger individuals. The Cancer Immunology Program will tackle the question of how spatial cues determine treatment resistance and accelerated cancer onset, with the ultimate goal of informing the next generation of cancer therapies.

 

Ana C. Anderson, PhD

Program Lead

Ana C. Anderson, PhD
  • Albert H. Coons Professor of Neurology, Harvard Medical School
  • Scientist, Brigham and Women’s Hospital
  • Core Faculty, The Gene Lay Institute Institute
  • Member, Broad Institute of MIT and Harvard
  • Co-chair, Infectious and Immunologic Disease Program, Brigham Research Institute

Dr. Anderson obtained her B.S. in Microbiology and Immunology from the University of Miami, where she graduated summa cum laude. She obtained her Ph.D. in Immunology from Harvard University in 1999.  During her Ph.D., she was awarded a fellowship from the Howard Hughes Medical Institute.

Dr. Anderson works in the fields of autoimmunity and cancer immunology, specifically on the regulation of the anti-tumor T cell response. Her laboratory identified that the co-inhibitory molecule Tim-3 is a key regulator of T cell dysfunction in cancer and has identified gene programs associated with activated, dysfunctional, and stem-like CD8+ T cell states in cancer.

Dr. Anderson has published over 65 original papers, 24 reviews, and 5 book chapters and has been recognized as a Highly Cited Researcher in Immunology since 2020 by Clarivate. Her work on T cell cross-reactivity in autoimmunity was selected by Nature Immunology as a ‘Classic Paper in Autoimmunity’. She has also had several papers selected as either ‘must-read’ or ‘recommended’ by the Faculty of 1000. Dr. Anderson is on the editorial board for OncoImmunology and The Journal for Immunotherapy of Cancer. She currently serves on the scientific advisory boards for Tizona Therapeutics, Trishula Therapeutics, Compass Therapeutics, Zumutor Biologics, ImmuneOncia, and Excepgen and is a paid consultant for iTeos Therapeutics and Larkspur Biosciences. Dr. Anderson’s research is funded by the NIH, non-profit foundations, and company sponsored research agreements.

Lab: https://anacandersonlab.com/

Kai W. Wucherpfennig, MD, PhD

Program Co-Lead

Kai W. Wucherpfennig, MD, PhD
  • Chair, Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute
  • Professor of Neurology, Brigham and Women’s HospitalProfessor of Immunology, Harvard Medical School
  • Nancy Lurie Marks Professor of Neurology in the Field of Medical Oncology, Harvard Medical School
  • Co-director, Parker Institute for Cancer Immunotherapy, Dana-Farber Cancer Institute

Dr. Wucherpfennig received a MD and PhD degree from the University of Göttingen in Germany and did his postdoctoral training at the Brigham & Women’s Hospital and at Harvard College.  He has been a faculty member at Dana-Farber since 1995.

His research focuses on the role of cytotoxic T cells and NK cells in cancer immunotherapy.  His lab studies mechanisms of resistance to cancer immunotherapies and develops novel immunotherapy approaches based on these molecular insights.  He discovered that human tumor-infiltrating T cells highly upregulate the inhibitory CD161 receptor and developed a blocking mAb that greatly enhances T cell and NK cell function.  A CD161 mAb is being evaluated in a first-in-human clinical trial (NCT05565417). Tumors also evade attack by T cells and NK cells through proteolytic shedding of stress proteins (MICA and MICB) recognized by the activating NKG2D receptor.  His lab designed mAbs that inhibit MICA/B shedding, unleashing immunity against metastatic disease.  This strategy is currently being tested in a phase 2 clinical trial (NCT05117476).

Dr. Wucherpfennig has served in a number of leadership roles in cancer immunology at DF/HCC and DFCI. He has been a co-leader of the Cancer Immunology Program of DF/HCC since 2004. He was appointed as chair of the Department of Cancer Immunology and Virology in 2015.  He has been elected as a member of the American Society for Clinical Investigation (2006), the Henry Kunkel Society at Rockefeller University (2007) and as Fellow of the American Society for the Advancement of Science (2009).

Lab: https://t-cells-treating-cancer.dana-farber.org/

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