학술논문

Heterogeneity in functional genetic screens: friend or foe?
Document Type
article
Source
Frontiers in Immunology, Vol 14 (2023)
Subject
heterogeneity
CRISPR-Cas9
genetic screens
therapy resistance
TNF
Immunologic diseases. Allergy
RC581-607
Language
English
ISSN
1664-3224
Abstract
Functional genetic screens to uncover tumor-intrinsic nodes of immune resistance have uncovered numerous mechanisms by which tumors evade our immune system. However, due to technical limitations, tumor heterogeneity is imperfectly captured with many of these analyses. Here, we provide an overview of the nature and sources of heterogeneity that are relevant for tumor-immune interactions. We argue that this heterogeneity may actually contribute to the discovery of novel mechanisms of immune evasion, given a sufficiently large and heterogeneous set of input data. Taking advantage of tumor cell heterogeneity, we provide proof-of-concept analyses of mechanisms of TNF resistance. Thus, consideration of tumor heterogeneity is imperative to increase our understanding of immune resistance mechanisms.