For de som er interessert:
- PCI + vaksine
- CD8 + CD4
- Hot tumors vs Cold tumors
Vaccine‐Based Immunotherapy for Head and Neck Cancers
Belgia
Received: 9 November 2021 Accepted: 28 November 2021 Published: 30 November 2021
Another area of emerging research aims to increase the immunogenicity of therapeutic vaccines. One technique under investigation is photochemical internalization (PCI). This technique uses the concomitant administration of a vaccine and a photosensitizer.
The photosensitizer, once illuminated, lyses the membrane of endosomal vesicles by se‐ creting very locally reactive oxygen species and releasing the contents into the cell’s cytosol (such as a DNA, RNA, or peptide vaccine). In in vitro experiments, the concomitant use of PCI with a short peptide increases the number of MHC I‐peptide complexes on the surface of DCs. In addition, stimulation of CD8+ antigen‐specific T cell proliferation was 30‐ to 100‐fold more effective with the concomitant use of PCI and the peptide vaccine versus the peptide alone. Furthermore, the authors demonstrated the presence of a strong increase (greater than 10‐fold increase in the median percentage) in HPV‐directed CTLs in mice vaccinated with PCI and the HPV16 E7 peptide compared to mice vaccinated with the HPV16 E7 peptide alone [116]. In a first phase I study (NCT02947854) [117], the fima‐ Vacc vaccine, combining PCI therapy, a TLR agonist, and an HPV16 E7 peptide, was well tolerated in healthy participants. ELISpot and flow cytometry demonstrated the presence of CD4+‐ and CD8+‐specific HPV T cells following vaccination.
Patients with “hot tumors” seem to currently have a more favorable outcome. These tumors are defined as being in an inflammatory microenvironment with a high immune gene expression signature, high level of tumor‐invasive T‐lymphocytes (TIL), a strong tu‐ mor expression of PD‐ligand(L)1, and a high mutational or neoantigen burden. Several studies have highlighted that HNSCC with a high level of TIL invasion, or high expres‐ sion of immune‐related genes, has a better overall survival, disease‐specific survival, and disease‐free survival.
These non‐independent markers differ from “cold tumors” that respond poorly to ICIs and are associated with poor survival. To increase efficacy, prognostic tools and new immunomodulatory strategies or treatment combinations are of interest.
Link: https://mdpi-res.com/d_attachment/cancers/cancers-13-06041/article_deploy/cancers-13-06041.pdf