Trained immunity of myeloid cells and their progenitors in patients with non-medullary thyroid carcinoma, colon carcinoma and melanoma

Non-medullary thyroid carcinoma (TC) is the most common endocrine malignancy
and its incidence is one of the most rapidly increasing among the cancer types.
For many patients with advanced and poorly differentiated tumors, treatment
options are limited and the prognosis of advanced stage metastatic disease
remains poor. Also the incidence of colon carcinoma (CC) has been increasing in
the past decades. In 2020 more than 8400 were diagnosed with CC in the
Netherlands. Although survival has improved in the last years, in 2011-2018 the
5-year survival rate was still only 67%. Likewise, the incidence of melanoma
has significantly increased in the last decades. In 2021, more than 7500
patients were diagnosed with melanoma in the Netherlands. Survival is excellent
in patients with localized disease, but poor for patients who develop distant
metastases. In those patients, 5-year survival is only 30% in patients with
stage IV disease.
Tumor-related inflammation is one of the hallmarks of cancers in general.
Innate immunity specifically is a common denominator which is involved in the
pathogenesis of both TC and CC. In a previous study (NL62671.091.17), changes
in the programming of myeloid immune cells and a possible role of their bone
marrow progenitors were identified in TC patients. To improve the patient*s
outcome and identify novel therapeutic targets, one needs a deeper
understanding of the tumor-induced changes in the bone marrow myeloid
progenitor cells. Furthermore, treatment of these cells by nanoparticles or
other agents that induce a program of *trained immunity* may be a novel way to
re-educate myeloid cells and their bone marrow progenitors in TC patients.
Lastly, we expect that this approach could be effective also in other cancers
of which CC and melanoma are here proposed as an additional model.
Hypothesis:
We hypothesize that by exposing myeloid cells or their progenitors to various
agents that induce trained immunity (e.g. HDL-MDP nanoparticles, recombinant
and synthetic cytokines), these immune cells will undergo functional
reprogramming to induce a tumor-suppressive phenotype. In the future, this
could be explored as a novel immunotherapy for tumors that are refractory to
conventional treatment.

To assess the transcriptional, epigenetic and functional reprogramming of
circulating monocytes and BM myeloid progenitor cells in TC, CC and melanoma
before and after in vitro exposure to agents that induce trained immunity.

investigator-initiated, single-center cross-sectional explorative study which
will be performed in the Radboud UMC Nijmegen

There are no risks associated with the study. There are no interventions other
than those related to the regular patient care except for a bone marrow
aspiration that will take place during surgery. The burden for the patients
will be maintained to a minimum. They will only be required to donate one blood
sample and a small sample of their during surgery removed tissue. ïo minimize
the discomfort, the bone marrow sample will be collected during the same
surgery under general anesthesia.