Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction (vol 411, pg 1058, 2001)

Citation
Af. Ochsenbein et al., Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction (vol 411, pg 1058, 2001), NATURE, 413(6852), 2001, pp. 183-NIL_21
Citations number
31
Categorie Soggetti
Multidisciplinary,Multidisciplinary,Multidisciplinary
Journal title
NATURE
ISSN journal
00280836 → ACNP
Volume
413
Issue
6852
Year of publication
2001
Pages
183 - NIL_21
Database
ISI
SICI code
0028-0836(20010913)413:6852<183:ROTLSS>2.0.ZU;2-K
Abstract
The vertebrate immune system has evolved to protect against infections that threaten survival before reproduction. Clinically manifest tumours mostly arise after the reproductive years and somatic mutations allow even otherwi se antigenic tumours to evade the attention of the immune system(1-3). More over, the lack of immunological co-stimulatory molecules on solid tumours c ould result in T-cell tolerance(4-8); that is, the failure of T cells to re spond. However, this may not generally apply(9,10). Here we report several important findings regarding the immune response to tumours, on the basis o f studies of several tumour types. First, tumour-specific induction of prot ective cytotoxic T cells (CTLs) depends on sufficient tumour cells reaching secondary lymphatic organs early and for a long enough duration. Second, d iffusely invading systemic tumours delete CTLs. Third, tumours that stay st rictly outside secondary lymphatic organs, or that are within these organs but separated from T cells by barriers, are ignored by T cells but do not d elete them. Fourth, co-stimulatory molecules on tumour cells do not influen ce CTL priming but enhance primed CTL responses in peripheral solid tumours . Last, cross priming of CTLs by tumour antigens, mediated by major histoco mpatibility complex (MHC) class I molecules of antigen-presenting host cell s, is inefficient and not protective. These rules of T-cell induction and m aintenance not only change previous views but also rationales for anti-tumo ur immunotherapy(1,2).