
Harnessing cancer immunotherapy during the unexploited immediate perioperative period
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ABSTRACT The immediate perioperative period (days before and after surgery) is hypothesized to be crucial in determining long-term cancer outcomes: during this short period, numerous
factors, including excess stress and inflammatory responses, tumour-cell shedding and pro-angiogenic and/or growth factors, might facilitate the progression of pre-existing micrometastases
and the initiation of new metastases, while simultaneously jeopardizing immune control over residual malignant cells. Thus, application of anticancer immunotherapy during this critical time
frame could potentially improve patient outcomes. Nevertheless, this strategy has rarely been implemented to date. In this Perspective, we discuss apparent contraindications for the
perioperative use of cancer immunotherapy, suggest safe immunotherapeutic and other anti-metastatic approaches during this important time frame and specify desired characteristics of such
interventions. These characteristics include a rapid onset of immune activation, avoidance of tumour-promoting effects, no or minimal increase in surgical risk, resilience to stress-related
factors and minimal induction of stress responses. Pharmacological control of excess perioperative stress–inflammatory responses has been shown to be clinically feasible and could
potentially be combined with immune stimulation to overcome the direct pro-metastatic effects of surgery, prevent immune suppression and enhance immunostimulatory responses. Accordingly, we
believe that certain types of immunotherapy, together with interventions to abrogate stress–inflammatory responses, should be evaluated in conjunction with surgery and, for maximal
effectiveness, could be initiated before administration of adjuvant therapies. Such strategies might improve the overall success of cancer treatment. Access through your institution Buy or
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THE CONTEXT OF STRESS Article 13 October 2023 STRESS AND CANCER: MECHANISMS, SIGNIFICANCE AND FUTURE DIRECTIONS Article 10 September 2021 THERAPY RESISTANCE: OPPORTUNITIES CREATED BY
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Immunol._ 5, e70 (2016). Google Scholar Download references ACKNOWLEDGEMENTS The authors thank the US National Cancer Institute (NCI), the Israel Ministry of Science and the Israeli Science
Foundation for research funding. REVIEWER INFORMATION _Nature Reviews Clinical Oncology_ thanks Bernhard Riedel, Daniel Sessler, Marie-Odile Parat and Rebecca Auer for their contribution to
the peer review of this work. AUTHOR INFORMATION Author notes * These authors contributed equally: Pini Matzner, Elad Sandbank. AUTHORS AND AFFILIATIONS * Neuro-Immunology Research Unit,
School of Psychological Sciences, Tel-Aviv University, Tel Aviv-Yafo, Israel Pini Matzner, Elad Sandbank & Shamgar Ben-Eliyahu * Department of Hematology and Oncology, Kaiser Permanente
Northern California, San Francisco, CA, USA Elad Neeman * Surgical Department, Yitzhak Shamir Medical Center, Be’er Ya’akov, Israel Oded Zmora * Department of Anesthesiology and
Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Vijaya Gottumukkala * Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel
Shamgar Ben-Eliyahu Authors * Pini Matzner View author publications You can also search for this author inPubMed Google Scholar * Elad Sandbank View author publications You can also search
for this author inPubMed Google Scholar * Elad Neeman View author publications You can also search for this author inPubMed Google Scholar * Oded Zmora View author publications You can also
search for this author inPubMed Google Scholar * Vijaya Gottumukkala View author publications You can also search for this author inPubMed Google Scholar * Shamgar Ben-Eliyahu View author
publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS All authors contributed equally to all aspects of the article. CORRESPONDING AUTHOR Correspondence to
Shamgar Ben-Eliyahu. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard
to jurisdictional claims in published maps and institutional affiliations. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Matzner, P., Sandbank, E.,
Neeman, E. _et al._ Harnessing cancer immunotherapy during the unexploited immediate perioperative period. _Nat Rev Clin Oncol_ 17, 313–326 (2020). https://doi.org/10.1038/s41571-019-0319-9
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