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Despite significant efforts to improve treatments, many types of cancer remain incurable. For this reason, researchers are not only focused on improving existing therapies but are also exploring novel approaches. One promising new direction lies within our own bodies: the immune system, which protects us daily from a wide range of diseases. Increasingly, research is directed towards harnessing the immune system to fight cancer, particularly using T cells. A fraction of T cells can effectively recognize tumor cells and subsequently kill these tumor cells via their receptors. These receptors can be used to transform non-tumor recognizing T cells into tumor recognizing cells, for instance, using so-called bispecific molecules or by genetically modifying cells.

In this thesis, we have investigated a specific type of T cell, the γδT cell, and its potential as an immunotherapy against cancer. We aimed to improve current γδT cell-based therapies and demonstrate the unique therapeutic potential of γδT cells in two types of solid tumors. First, we explored ways to enhance the efficacy of our γδT cell-based bispecific molecules, named GABs, and we observed that when we increase the binding of the GABs to the tumor, we found a more beneficial therapeutic success. The improved therapeutic success could also be reproduced in a different γδT cell-based therapy, genetically modified cells called TEGs. Furthermore, we examined the potential of distinct γδT cell subsets in glioblastoma and proposed strategies to overcome potential glioblastoma escape mechanisms. Lastly, we studied the role of γδT cells in colorectal cancer, which yielded novel insights for future treatment approaches. Altogether, our findings contribute to the broader understanding of γδT cells and their receptors and offer new opportunities for improving existing therapies and developing innovative immunotherapeutic strategies against cancer.