Professor Shubhada Chiplunkar is a distinguished immunologist and researcher with over 40 years of experience in cancer biology and immunology. She is the former Director of the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) at the Tata Memorial Centre in Navi Mumbai, where she also led the Cancer Immunology and Immunotherapy Research Group.
Prof Chiplunkar obtained her PhD from the University of Mumbai in 1983 and completed her post-doctoral fellowship at the Max Planck Institute for Immunology in Freiburg, Germany. Her research focuses on understanding immune dysfunctions in the tumour microenvironment of cancer patients and developing immunotherapeutic strategies using gamma delta (γδ) T cells. Dr Chiplunkar has made significant contributions to the field of cancer immunotherapy, particularly in deciphering the role of tumour microenvironment in shaping anti-tumour γδ T cell responses in various malignancies.
Prof Chiplunkar is a member of several scientific advisory and review committees of national research institutes. Currently, she is the President of the Immuno-oncology Society of India (IOSI) and the Mumbai Immunology Group (MIG), and a member of the International Union of Immunological Societies (IUIS) Education (EDU) Committee.
What inspired you to pursue a career in immunology?
During my undergraduate days while studying Microbiology, my exposure to Immunology was minimal. Later, when I joined the Cancer Research Institute, TATA Memorial Centre, Mumbai for a PhD program where my project was ‘Studying immune responses in mice exposed to endogenous and exogenous murine mammary tumour viruses.’ This triggered my interest in learning and pursuing basic immunology.
I then joined Prof. Stefan Kaufmann’s lab at the Max Planck Institute of Immunobiology at Freiburg, Germany, (MPI Freiburg) on a Post Doctoral fellowship. We were investigating the role of cytotoxic CD8 T Cells in mycobacterial infections, particularly in M. leprae infected mice. How the leprosy bug influenced the host immune system was not well understood.
Generating M. leprae specific cytotoxic T-cell clones that kill M. leprae infected macrophages was challenging, given the fact that M. leprae did not stimulate host’s immune responses. The initial setbacks in establishing the T Cell clones pushed me to delve deep into understanding how the participating immune cell types function and cross talk.
Moreover, MPI Freiburg had a fascinating scientific atmosphere that was inspiring to a young immunologist like me. Discussions with my mentor Prof Stefan and my colleagues were enjoyable and enriching and I returned to India with the firm determination to pursue a career in Immunology.
Can you share a pivotal moment in your career that significantly influenced your research direction?
After my post-doc I joined the Cancer Research Institute, Tata Memorial Centre in Mumbai on a staff scientist position to work on an anti-leprosy vaccine in multi drug resistant (MDR) leprosy patients.
The work involved visits to leprosy hospitals, vaccine trial areas in Mumbai and rural areas of the state of Maharashtra to collect clinical samples for our study. This was my first interaction with patients and their families. Reading about the pathogenesis and clinical manifestation of the disease from published literature, is vastly different from witnessing the real-world scenario. The suffering these patients undergo, and the social stigma associated with the disease is hard to comprehend. These patients were willing to share clinical samples and gave their consent with the trust and belief that they and their families would be freed of this disease. This was the turning point in my career that compelled me to make judicious decisions regarding my research projects. Knowing well the challenges, I decided that I would work on projects with the potential to get translated to clinical applications.
After becoming an independent group leader, we started investigating the role of γδ T cells in patients with solid tumours and leukaemia. Integrating basic immunology knowledge to address vexing clinical questions has always remained my research focus.
How do you see the role of γδ T cells evolving in Cancer immunotherapy?
γδ T cells once labelled as enigmatic and ignored are currently receiving the coveted status as forerunners of antitumor immunity. The non-MHC restricted feature of antigen recognition make them attractive candidates for allogenic γδ T cell based therapy. γδ T cells are frequently observed infiltrating multiple tumour types and serve as favourable prognostic biomarkers (Vd1 subset).
Clinical trials using γδ T cells (unmodified or engineered CAR γδ T cells) against various malignancies, including solid tumours and haematological malignancies is gaining momentum. Several protocols are available for ex vivo expansion of γδ T cells in large numbers for clinical use. Synthetic grade phosphoantigens or aminobisphosphonates (Zoledronate) in combination with cytokines IL2, IL15 are being used to expand these cells. Ex vivo expanded Vd1 cells (DOT) cells are undergoing clinical testing in AML patients and are also amenable to engineered CAR-T cell therapies. Other therapeutic strategies include antibody based bispecific engagers using Vd1, Vd2 T cells or use of agonistic anti BTN3A1 (ICT01) antibodies to activate γδ T cells. Although preliminary readouts of clinical trials using γδ T cells look promising, in-depth investigations are needed to understand the in vivo persistence of adoptively transferred γδ T cells and their ability to perform anti- tumour effector functions in a complex tumour microenvironment.
Can you discuss a recent breakthrough in your research about which you are particularly excited?
In research, there are often several moments that can be exciting, and these euphoric moments prompt us to pursue what we have been doing with greater passion and commitment. I initiated projects on γδ T cells in my lab way back in 1992. Ours is the first lab in India to address the role of these cells in cancer patients (head and neck, oesophageal, breast, colon, gall bladder and in acute lymphoblastic leukaemia). During those days it was challenging to cultivate, expand and characterise γδ T cells from tumour and blood of cancer patients and study their functions as there were limited antibody/gene probes available and access to Flow cytometers was limited.
Despite the difficulties encountered, we published our first manuscript on how γδ T cells isolated from Oral Cancer, patients recognise heat shock protein 60 on oral tumour cells and are able to lyse these cells. This moment I will always cherish, as will my students who collaborated with me on the project. Since then, my group has been engaged in deciphering role of the tumour microenvironment in shaping the γδ T cell repertoire, phenotype, and function, how Notch signalling regulates their effector functions and how these cells differentiate into pro-tumour Tγδ17 cells and the profound effect of hypoxia on their anti-tumour function. We also studied the epigenetic regulation of γδ T cells and their cross talk with myeloid derived suppressor cells (MDSC) and osteoclasts. Addressing each of these questions was exiting, and obtaining meaningful data that improved our understanding of the role played by these cells in defence against cancer was a breakthrough in our journey.
How do you balance your role as a researcher, educator, and leader in the scientific community?
To be a researcher and an educator, you need to have a penchant for doing both. Good Researchers are not always good educators. Time management is the key when you must balance your role as a Researcher, PhD mentor, Teacher, and Administrator. In my case being a Researcher, Group leader and later as Director of the Institute required careful time management that involved working late hours during the week and partly on weekends. In a Research Institute like ours my role as an educator included mentoring PhD students, teaching associated with their course work, conducting evaluations, attending student seminars. Managing student activities as Chairperson of the Academic Program at the Institute also included my participation as council member of the University to make policy decisions.
To be a good teacher it is extremely important to have a good understanding of the subject, which involves keeping abreast of newer developments in the field. Since my research interests and teaching involved related topics, it became easier to integrate both.
As you climb up the ladder in your career, the increase in the administrative workload makes it challenging to dedicate more time to your students who prefer one-on-one interaction. This is only possible if you are willing to dedicate additional time beyond regular working hours.
I have always enjoyed teaching and realised that the undergraduate students are deprived of good immunology teaching. To meet this demand, I established the Mumbai Immunology Group, and we formed a team of scientists who were willing and interested in devoting their time to teaching undergraduate and post graduate students at different colleges of Mumbai. We also conducted ‘Teacher Training workshops.” In short, I strongly believe “If there is a will, there is a way.”
How do you stay motivated and inspired in the face of setbacks and challenges?
I am sure every Researcher has faced challenges and setbacks in their career. It may happen that the ideas you have in mind do not work out the way you expected. It results in delay in planned project work, wasting precious man hours, time, and money. I have always looked at it as a transient phase. It is important to learn from the mistakes and keep an open mind to accept the failures. Staying focused and persistent has helped me in such situations.
What role do you think public awareness and education play in the fight against cancer?
Cancer has remained a global health challenge. Public awareness and early detection make a significant difference in reducing the burden of the disease and increase survival rates. Factors such as educational status, rural-urban disparities contribute to the knowledge gap of cancer awareness. Screening is an important preventive measure of cancer control. Cancers such as Cervical, Breast, Colon, Prostate can be detected early through screening programs. Promoting healthy lifestyles, cessation of tobacco and limited alcohol consumption can help in preventing cancers of oral cavity, lung etc.
What advice would you give to young scientists aspiring to enter the field of cancer immunotherapy?
Cancer Immunotherapy is in the limelight today as an important treatment modality. Students interested in pursuing a career in this field need to have a good background training in basic immunology. Today, Immunology has emerged as a separate discipline and post-graduate degree courses are offered by various universities. An opportunity to work as a Project Trainee in a lab engaged in cancer immunology research would be the best training exposing one to cutting-edge basic, preclinical, or clinical research. For Medical students /physician scientists it is important to have the clinical experience in design and conduct of clinical trials. Engineered cell and antibody-based therapies are in the forefront of cancer treatment modalities. Resilience and adaptation to newer technologies appears to be important in the fast evolving field of cancer immunotherapy. Willingness to change career paths to integrate omics technologies, computational biology, nanomedicine, bioengineering are other options that find application in advancement of Cancer Immunotherapy.
What do you envision for the IUIS EDU Committee in the next 10 years? How do you think teaching and learning will change?
Education is undergoing a transformative change. Virtual classrooms with personalized teaching are already replacing the current chalk -board approach to smart screens. The role of teachers will begin to trend more towards mentors as a clear change in their role from primary information givers to facilitators. Artificial intelligence (AI), online learning and breakthrough technologies like virtual and augmented reality (AR/VR) have already permeated our education system. The next decade will witness education transformed by technological advancements with a renewed focus on adaptability and inclusion. The IUIS EDU committee must adapt to this change and leverage the use of these modern tools to decentralize education, create virtual laboratories and build an ecosystem to link and network teachers across the globe with students from all corners and make learning an enjoyable experience. Beyond didactic learning and skill teaching the next generation is also likely to benefit from cross disciplinary fertilization and thus IUIS EDU committee activities could engage emerging fields such as systems biology, computational biology, nano technology, bioengineering etc.
Professor Shubhada Chiplunkar – shubhachiplunkar@gmail.com
Interview by Bonamy (Bon) Holtak
