Secondary lymphoid organs are integral to initiation and execution of adaptive immune
responses. These organs provide a setting for interactions between antigen-specific
lymphocytes and antigen-presenting cells recruited from local infected or inflamed
tissues. Secondary lymphoid organs develop as a part of a genetically preprogrammed
process during embryogenesis. However, organogenesis of secondary lymphoid tissues
can also be recapitulated in adulthood during de novo lymphoid neogenesis of tertiary
lymphoid structures (TLSs). These ectopic lymphoid-like structures form in the inflamed
tissues afflicted by various pathological conditions, including cancer, autoimmunity,
infection, or allograft rejection. Studies are beginning to shed light on the function of
such structures in different disease settings, raising important questions regarding their
contribution to progression or resolution of disease. Data show an association between
the tumor-associated TLSs and a favorable prognosis in various types of human cancer,
attracting the speculation that TLSs support effective local antitumor immune responses.
However, definitive evidence for the role for TLSs in fostering immune responses in vivo
are lacking, with current data remaining largely correlative by nature. In fact, some more
recent studies have even demonstrated an immunosuppressive, tumor-promoting role
for cancer-associated TLSs. In this review, we will discuss what is known about the
development of cancer-associated TLSs and the current understanding of their potential
role in the antitumor immune response