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On the frontier of immunogerontology—an interview with Prof. Graham Pawelec
* Corresponding author: Xiaodong Li, PhD
Mailing address: The Africa Hepatopancreatobiliary Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, FL, USA.
Email: shuiliuhefang@163.com
Accepted: 08 August 2022 / Published: 30 September 2022
DOI: 10.31491/APT.2022.09.094
Abstract
The article is an interview with Prof. Graham Pawelec of the Department of Immunology at the University of Tübingen, conducted by Xiaodong Li of the Mayo Clinic African Hepatobiliary Cancer Consortium (AHPBCC), on behalf of Aging Pathobiology and Therapeutics.
Graham Pawelec, PhD
Graham Pawelec received an MA in Natural Sciences in
1978 and a PhD in Transplantation Immunology in 1982
from the University of Cambridge, UK, and the Dr. habil
and Venia Legendi from the University of Tübingen, Germany, where he became Professor of Experimental Immunology in 1997. From 1999 to 2017 he led the Tübingen
Ageing and Tumour Immunology (TATI) group within the
Second Department of Internal Medicine, University of
Tübingen Hospitals System. He remains affiliated part-time
Faculty at the Department of Immunology, University of
Tübingen. He is currently affiliated with the Cancer Solutions Program, Health Sciences North Research Institute
of Canada, Sudbury, ON, and is a Visiting Professor at
Nottingham Trent University, UK, King´s College London,
London, UK, and is an Honorary Professor at Manchester
University, UK.
Xiaodong Li: Let’s have everyone get to know you first,
can you tell us how you got into the field of immunology
research and where were your early passions?
Graham Pawelec: After studying a mixture of preclinical
and biology subjects as an undergraduate at Cambridge
University (which did not have a Clinical School at that
time), I stayed in Cambridge and graduated with a History
& Philosophy of Science, MA 1976 (Cambridge was the
only British University offering this specialty at that time).
Although I retain an interest in this fascinating topic, I
felt that I needed to do something of more practical relevance to humanity and so embarked on a job as Research
Assistant in the Dept. Surgery at Cambridge, which was
pioneering solid organ transplantation and immunosuppression at that time. This was on the front lines of medical interventions to save lives and was very exciting in
the late 1970s. I registered for a Ph.D., finally submitted
in 1982, four years after I left Cambridge and moved to
Germany to continue work in human transplantation - but
in the even more demanding and difficult area of bone
marrow transplantation for leukemia (Tübingen was one
of the first medical schools in the country to set up a BMT
unit). This aroused our interest in anti-tumor immunity in
general due to the anti-leukemia effects of the transplant;
culturing T cells in vitro for adoptive immunotherapy and
use as agents for tissue matching then aroused interest in
the aging of cells in culture, and eventually in immune
aging in general. And after all these years, the issues of
specific transplantation tolerance, anti-cancer immunity,
immunosenescence, and vaccination efficacy in the elderly are all still open and exciting and crucial for enhancing the health and longevity of older adults worldwide. So
that is still my passion.
Xiaodong Li: You have a legendary career. You achieved
great success in multiple countries. Can you share your
experience in achieving that?
Graham Pawelec: Actually, I have been very sessile,
based only in Cambridge, and then for more than 40 years
in Germany. My work in Canada and visiting professorships in the UK did not involve lengthy stays, but mostly
shorter-term visits. Nonetheless important for collaborations and mentoring, especially the Canadian collaboration
on influenza vaccination in the elderly. Very important to
have international collaborations. It is crucial to be able to
maintain these across borders that do not exist in science.
Xiaodong Li: Much of your work has remained centered
on immunogerontology, vaccination, and cancer immunology/immunotherapy. What are some highlights of your
research findings in this field?
Graham Pawelec: 1. My earliest contributions were addressed to transplantation immunology and how to prevent graft rejection and induce immunological tolerance.
We were the first to demonstrate the immunosuppressive
properties of Cyclosporin A and that it preferentially inhibited T cells, not B cells. The introduction of this newgeneration immunosuppressive agent revitalized organ
transplantation in Cambridge and allowed the re-introduction of pediatric kidney transplantation.
2. We pioneered techniques to establish long-term cultured human T cell clones (TCC) and undertook extensive
characterization of their properties in vitro. We established
that such clones possessed finite lifespans in culture (unexpected at the time). In attempts to parallel longitudinal
in vitro models of immune aging during long-term culture
of TCC, we began to analyze younger and older people
for characteristics of immunosenescence. Using the biomarkers established from cultured TCC, we asked which
were also seen ex vivo. Early on, this drew our attention
to the role played by a chronic viral infection, especially
and unexpectedly with the common herpesvirus Cytomegalovirus (CMV). We hypothesized that chronic antigenic
stimulation “exhausted” T cell immunity and that this
could contribute to decreased immunosurveillance against
pathogens and cancer. We showed that CMV was part of a
cluster of simple immune parameters predicting survival
in the very elderly, the “Immune Risk Profile” (IRP). We
studied this in the context of different populations and ethnicities, and under different circumstances (e.g., variable
socioeconomic status, psychosocial status, health status).
We have examined these issues in well-characterized European (Germany, Holland, Belgium, Sweden, Britain)
and non-European (Pakistan, Singapore) populations.
3. When performing immune monitoring studies of cancer
patients undergoing experimental immunotherapies, we
were aware of the potential impact of age and CMV on
immunocompetence potentially impinging on the success
or failure of such therapies. We showed that the melanoma patients´ functional T cell responses against certain
tumor antigens predicted survival. Together with assays of
regulatory T cells and myeloid-derived suppressor cells,
these studies began to provide powerful tools for predicting patient outcomes and stratifying responders and nonresponders. We recently extended these studies to breast
cancer patients—specifically, investigating older women
and showing that their “immune signatures” measured
as outlined above also predicted survival, as they did for
younger patients.
4. In the context of vaccination, as well as our contributions in the cancer immunotherapy field, including the
first study to show a clinical benefit of multi-peptide
vaccination in renal cancer patients, we dissected the
detrimental effect of age-vs-CMV infection on influenza
vaccination in the elderly. These studies included findings
on the influence of CMV infection on antibody responses
of older people to the first seasonal influenza vaccine to
be licensed specifically for use in the elderly and studies
directed at identifying mechanisms responsible for weaker
memory responses to viral core proteins.
Xiaodong Li: Can you share with us your current focus and
what you most want to achieve?
Graham Pawelec: Currently, I am focusing on mentoring, consulting, editing, and reviewing. These interactions
range from work in mentoring programs such as that of
the Gerontological Society of America, and the new peerreview mentoring program of the Society for Immunotherapy of Cancer (very important in my view) to consulting for biotech startups, reviewing grant and fellowship
applications for international bodies, and attempting to
teach colleagues and doctors that the immune systems
of older adults are not intrinsically incapable of responding adequately to vaccines as is commonly believed. I
am arguing for a paradigm shift away from the “received
wisdom” that immunosenescence is inevitably responsible
for decreased responses to vaccination, and for increased
susceptibility to infectious disease and cancer–especially
for the latter there is very little actual evidence.
Xiaodong Li: You continue to publish highly impactful
work over your long career. Any advice for junior colleagues on how to build and maintain that productivity for
so long?
Graham Pawelec: I think that if someone is enthusiastic
about science and discovery from a young age, this never
changes over the years. Experimental science is not “just
another job” - it demands sacrifice, social and often financial, and someone who is not fully committed to an ongoing uphill battle should consider a different career from
the beginning.
Xiaodong Li: At what point in your career did you begin to
get involved with editorial roles?
Graham Pawelec Mid-level, I guess. My first Editorial
Board membership invitation was some time around 1990
I guess.
Xiaodong Li: (Follow up) Do you think it’s beneficial for
early career investigators? If yes, Any advice to help junior faculty/early career researchers obtain editorial roles?
Graham Pawelec: I think it is essential to learn how to act as a competent peer reviewer, starting at the predoctoral
level. Reliable work for a particular journal may then
eventually result in a meaningful invitation to join the
Board. However, Board membership has less meaning
nowadays when journals invite anyone who has acted as
an ad hoc reviewer to join the Board and end up with hundreds of members. Editing special issues may still be of
interest if the guest editor can solicit invitations and oversee the reviewing process, but this would usually require
more seniority.
Xiaodong Li: Thank you, Prof. Pawelec. Lastly, I would
like to take the chance to thank you for mentoring and advising us.
Graham Pawelec: Thank you for asking.