Sheila Ganti

Interdisciplinary Training

Sheila Ganti

"Lymph node alterations in melanoma"

A functioning immune system must be able to definitively distinguish foreign from self; failure to do so
can result in autoimmune disorders. This issue also comes into play in the case of cancer. Despite the
fact that tumors originate from the body?s own tissue, in some instances the immune system is able to
successfully recognize and eliminate the cells making up the cancerous mass. For the majority of clinical
cases, however, the tumor avoids detection and continues to grow. Understanding the immune
alterations that promote tumor growth and subsequent dissemination is required. We have previously
identified structural and immunological alterations in lymph nodes draining lymphomas and cutaneous
melanomas in murine models. Tumor draining lymph nodes (TDLNs) exhibited large scale B cell
accumulation and increased lymphatic sinus growth (lymphangiogenesis). The absence of B cells but not
T cells prevented lymphangiogenesis. Cutaneous melanoma implanted in the footpad of mice lacking B
cells also grew slower compared to tumors from mice with B cells. These data indicate a critical function
of accumulating B cells in the TDLN, and suggests novel roles for B cells in mediating tumor metastasis
and primary tumor. In this proposal, we aim to determine how these B cells are able to exert their effect
to not only promote lymphangiogenesis, but also to uncover their role in modulating primary tumor
growth. Findings from these studies may point to effective immunotherapies for many cancers.