Fig. 11
From: Advances in molecular pathology and therapy of non-small cell lung cancer
Resistance mechanisms underlying immunotherapy in NSCLC. Cancer immunotherapy may involve some of the most complex resistance mechanisms known, affecting nearly all cells, molecules, and pathways. The vast genetic and epigenetic abnormalities, estimated to involve approximately 1000 genes – including various cytokines, chemokines, protein kinases, and metabolic enzymes – result in T cells tolerating or coexisting with cancer cells. Therefore, we propose a new theoretical framework for understanding the mechanism of immunotherapy resistance, characterized by a dynamic and cyclical process: an equilibrium/balance favoring cancer cells (primary resistance), followed by treatment shifting the balance towards favoring immune cells, and eventually a re-establishment of equilibrium favoring cancer cells (secondary resistance) – which repeats over time
