OCTOBER 2, 2026, NEW YORK – Both the clinical effects and the unpleasant side effects of chemotherapies, from hair loss to mouth sores to gastrointestinal discomfort, stem from their indiscriminate destruction of cells prone to rapid proliferation. That includes CD8+ T cells, the body’s frontline soldiers against viral infections and cancer, which multiply furiously when they’re activated by their target antigens.
Now researchers led by Laurine Noblecourt, Amanda Wicki and Benoit Van den Eynde in the Van den Eynde laboratory at the Oxford Branch of the Ludwig Institute for Cancer Research, and former senior immunologist at the lab Carol Leung, who is now Group Leader at the NDM Centre for Immuno-Oncology, have uncovered a previously unknown mechanism by which chemotherapies can, somewhat paradoxically, boost therapeutic T cell responses. They describe in the current issue of Cancer Cell how the combination of carboplatin and paclitaxel (known as CarboTaxol) as well as cyclophosphamide can function as adjuvants—substances that amplify the effects of vaccines—boosting the efficacy of cancer vaccines in preclinical studies.
The researchers additionally show that this therapeutic effect is further enhanced when the combined regimen is supplemented with anti-PD-1 immune checkpoint blockade (ICB), an immunotherapy that prevents T cell exhaustion to intensify the T cell assault on tumors.
“Our studies demonstrate in preclinical models of cancer that, if correctly timed, the combination of these chemotherapies with a cancer vaccine can synergize with ICB to enhance tumor control and significantly extend survival,” said Leung. “This therapeutic effect stems from the direct modulation of key functional traits of CD8+ T cells by the chemotherapies, which enables a better response to subsequent vaccination and, possibly, to anti-PD-1 ICB as well.”
Since chemotherapies indiscriminately kill rapidly dividing cells, they can potentially compromise cancer immunotherapies. Yet studies have also shown that in some cancers chemotherapies can indirectly support ICB by depleting immune cells within tumors that suppress anti-cancer immune responses. Additionally, chemotherapies can stimulate such responses by exposing a variety of cancer antigens to the immune system when they kill cancer cells.
But how chemotherapies might affect vaccine-induced immune responses to tumors has not been methodically examined until now.
“Most clinical trials evaluating cancer vaccines administer the experimental therapy along with chemotherapy because chemo is standard-of-care,” said Noblecourt. “But they do so without reference to established evidence on how chemotherapies affect vaccine responses.”
To find out, the Ludwig Oxford team tested the effects of a panel of chemotherapies on the efficacy of a cancer vaccine developed by the Van den Eynde laboratory. The vaccine, which targets the non-human analogue of a common cancer antigen identified and characterized by Ludwig researchers, is delivered in two shots given days apart, known as the “prime” and “boost” doses.
CarboTaxol, the researchers found, improved the efficacy of the vaccine in several preclinical models of cancer when it was given with either dose of the vaccine.
“Chemotherapies enhanced vaccine-induced CD8+ T cell responses against the targeted cancer antigen, expanded the pool of tumor-targeting CD8+ T cells and extended survival in preclinical models,” said Noblecourt. “This effect was further enhanced by ICB.”
Timing, however, was everything. The adjuvant effect of CarboTaxol was only seen when it was administered on the same day as the vaccine. It was lost if the chemotherapy and vaccines were administered days apart.
The researchers show that CarboTaxol expands a pool of CD8+ T cells that express a factor known as TCF1. A master regulator of gene expression, TCF1 switches on genes that rejuvenate CD8+ T cells, extending their life, functionality and ability to establish an immunological memory of an encountered antigen.
“CD8+ T cells that express TCF1 are of critical importance to initiating and sustaining anti-cancer immune responses,” said Wicki. “The expansion of these cells by chemotherapy occurred independently of vaccination and established a deep pool of T cells for mobilization upon subsequent exposure to the vaccine antigen.”
In support of the clinical relevance of their findings, the researchers show that TCF1+ CD8+ T cell expansion could also be seen in samples taken from two independent cohorts of patients with different types of cancer who had been treated with CarboTaxol.
“Our findings have significant implications for clinical trials of cancer vaccines,” said Van den Eynde. “Current studies may not be taking advantage of a potential adjuvant effect that might be obtained by simply altering the timing of vaccination relative to chemotherapy. Our study paves the way to defining the optimal interval to induce such synergies. Further, because TCF1+ CD8+ T cells are important for optimal responses to ICB as well, the mechanism we’ve identified here may extend beyond vaccines to other immunotherapy combinations. At the very least, our findings support the clinical evaluation of the combination of cancer vaccine, chemotherapy and anti-PD-1 checkpoint blockade examined in this study.”
This study was supported by the Ludwig Institute for Cancer Research, the Berrow Foundation, the Swiss National Science Foundation and the Academy of Medical Sciences in the U.K.
Aside from being a Member of the Ludwig Institute for Cancer Research, Benoit Van den Eynde is director of the de Duve Institute and a professor of tumor immunology at the University of Oxford and at UCLouvain.
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About Ludwig Cancer Research
Ludwig Cancer Research is an international collaborative network of acclaimed scientists that has pioneered cancer research and landmark discovery for more than 50 years. Ludwig combines basic science with the translation and clinical evaluation of its discoveries to accelerate the development of new cancer diagnostics, therapies and prevention strategies. Since 1971, Ludwig has invested nearly $3 billion in life-changing science through the not-for-profit Ludwig Institute for Cancer Research and the six U.S.-based Ludwig Centers. To learn more, visit www.ludwigcancerresearch.org .
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Cancer Cell