It’s well established in the field of immuno-oncology that in
nearly all cancers, a subset of patients presents with an immune infiltrate. In
many of these tumors, the infiltrating immune cells appear to form aggregates
that are especially noticeable at the tumor periphery. Indeed, when presenting
my research on these aggregates at scientific meetings, I’ve often been
approached by other scientists or clinicians who indicate that they’ve seen
lymphoid aggregates in tumor tissue from their patients, but didn’t know to
investigate them further.
This brief overview may change some of those minds.
While multiparameter imaging can distinguish the features of TLS, they can more easily be
appreciated by H&E staining. (Interestingly, a genetic signature
based on chemokine expression can also be used to predict the presence of TLS
within tumors.) TLS resemble secondary lymphoid organs based on the presence of a germinal
center-like B cell aggregate and/or PNAd+ high endothelial venules surrounded
by a zone of T cells and dendritic cells. Lymphocytes are recruited into TLS via these high endothelial venules, as PNAd binds L-selectin/CD62L, which is found on the surface of both T cells as well as B cells. TLS are thought to be a site of local T cell priming,
independent of lymph nodes due to the ability of APC to recover antigen within
the tissue and present it to nearby T cells within the TLS.
Besides their prognostic value, TLS may provide a novel avenue
for therapeutic development. A recent publication from my lab demonstrated in a
murine model of colon cancer that TLS can be induced therapeutically by the introduction of Type 1-polarized
dendritic cells into the tumor microenvironment, and this is associated with
delayed tumor growth. Others have postulated that TLS-positive tumors may be
more responsive to immunotherapy because of the high density of T cell
infiltrate in these tumors, including regulatory T cells.
An understanding by scientists and clinicians that lymphoid
aggregates observed in tumors may have the hallmarks of TLS should help the
field better appreciate in which tumor types they are found, and what their
prognostic value may be. Simultaneously, while research into the benefit of
therapeutically targeting TLS is still in its early stages, a basic
understanding of these structures should help the field develop novel ways to
target them therapeutically, while taking into account other characteristics
such as tumor location, mutational status, and standard-of-care therapies for
various cancers.
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