Open Access
Table 1
Factors determining TIL product quality and clinical efficacy.
| Factor | Description | Impact on efficacy |
|---|---|---|
| TIL phenotype and differentiation state | Balance between stem-like/memory T cells (TCF-1+, CD28+, CD39−) and cytotoxic effector T cells [35, 36]. Excessive exhaustion (PD-1, TIM-3, LAG-3, CD39) limits function [33, 34]. | Stem-like TILs improve persistence and responses [37–39]; overly differentiated cells lack durability [40]. |
| Tumor specificity and reactivity | Higher proportion of TILs reactive to tumor antigens vs. bystander or suppressive cells (e.g., Tregs, DN TILs) is desirable [9, 29]. | Higher tumor-reactive fraction correlates with better outcomes [45]. Suppressive populations worsen efficacy [29, 43, 44]. |
| Infused cell dose | Number of TILs infused, typically in the range of 10–100 billion [48, 49]. | Higher doses generally correlate with better outcomes, but only within the context of quality TILs [46, 47]. |
| Persistence and in vivo expansion | Ability of infused TILs to survive, expand, and maintain function post-infusion. Dependent on phenotype, lymphodepletion, and host factors [35–40]. | Greater persistence is associated with durable responses and long-term tumor control [50]. |
| Exogenous cytokine support | High-dose IL-2 is standard but has significant toxicities (vascular leak, hypotension) and expands both effector T cells and Tregs [9, 52, 53]. | Supports TIL proliferation but with toxicity trade-offs. Alternative cytokines (e.g., IL-15, IL-7) are under investigation [56, 57]. |
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