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
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).