Local immunotherapy in cancer Flashcards
What is the benefit of low dose local immunotherapy?
High doses of immunotherapy can have adverse events, local low dose immunotherapy has the same effect but less auto-immunity side-efffects.
What is the effect of oncolytic viruses?
Oncolytic viruses only replicate in tumor cells which will result in tumor cell lysis. Are only effective if it leads to an immune reaction to the tumor cells.
Why is the activation and maturation of DCs important in tumors?
Antigen presentation of tumor antigens, TIL recruitment.
Why is the sentinel lymph node removed in cancer?
The SLN is the first draining lymph node so it has the most chance to have tumor cells in them.
What is in vivo vaccination?
In vivo vaccination is where you intratumorally inject a substance like an immune stimulatory agent or immune checkpoint inhibitor that can change the balance in immune-suppressing mechanisms in the TME so that it becomes more favorable to start an immune response. At the same time, there must be some antigen release so immunogenic cell death so that antigen and adjuvant can work together as in situ immunization process. This will lead to a response of effector T-cells that will spread throughout the body and provide systemic protection.
The advantage is that there is no knowledge needed of the expressed antigens from the tumor.
What are the 6 steps that are needed to effectively induce in vivo immunization?
- Change immunosuppressive TME to immunostimulatory (Checkpoint inhibitors, cytokines, TLR-L).
- Cause immunogenic tumor cell death and release TAs (chemotherapy, radiotherapy, oncolytic viruses).
- Recruit and activate APCs and increase TA uptake and processing by APCS (GM-CSF, TLR-L).
- Enhance antigen presentation to T cells by APCs and activate T cells (GM-CSF, TLR-L, anti-CTLA-4).
- Expand and recruit activated immune cells to kill treated tumor cells (NCTR, anti-PD-1, DCs, chemokines).
- Attack untreated tumors by circulating effector and memory T cells and generate long-term protection.
Where does the local efficiency of intratumoral immune therapy depend on?
The local efficiency of intratumoral immune therapy depends on active recruitment of immune effectors, maintenance of tissue-resident memory cells, destruction of immunosuppressive cell types, release of DAMPs and antigen presentation and activation of innate immunity (T-cells).
