Relationship of tumor leucocytic infiltration to host defense mechanisms and prognosis

Abstract

The interface between the tumor and the host is often the site of leucocytic infiltration. We will examine the idea that the infiltrating leucocytes of human and experimental tumors are components of the host immunological defense against the tumor, and that the presence of the infiltrate is a marker of favorable prognosis. Leucocytes could infiltrate tumors because of an active immune response, either nonspecific or specifically directed to tumor-associated antigens. Leucocyte influx may also occur because of chemotactic factors secreted by the tumor cells. Some tumors release factors which enhance vascular permeability and permit improved access by leucocytes to the tumor focus. The consequences of leucocytic infiltration include tumor cell cytolysis, cytostasis, or stimulation of proliferation. The present state of our knowledge of the interactions between tumor cells and infiltrating leucocytes precludes broad generalization of mechanisms. Further study will probably reveal that the mechanisms are diverse, and that there are some systems in which immune interactions occur at this interface and others in which they do not.

On the Role of Cell Surface Chondroitin Sulfates and Their Core Proteins in Breast Cancer Metastasis

“…This significantly slower growth rate in P-selectin deficient mice was unexpected because Pselectin is assumed to play a role in leukocytic infiltrates within tumors, which are generally inversely associated with tumor growth (Kreider et al, 1984). These findings, consistent with our hypothesis, demonstrate that the presence of P-selectin ligands on tumor cells and P-selectin-mediated interactions with stroma leads to tumorigenesis and tumor growth promotion.…”

Progressive loss of endothelial P-selectin expression with increasing malignancy in colorectal cancer

“…For example, leukocyte infiltration within tumors is generally associated with decreased tumor growth rate in carcinomas of the breast, stomach and colon. 18,[21][22][23] Our results suggest that in CRC, malignant progression of the tumor leads to progressive P-selectin down regulation. This phenomenon has been described also for other endothelial cell-associated adhesion molecules in colorectal tumors (ICAM-1, E-selectin).…”

Inducible heat shock protein 70 expression as a potential predictive marker of metastasis in breast tumors

“…Peripheral tolerance may explain the lack of response against tumor-specific antigens. The immune system, however, is capable of responding to breast cancer as evidenced by systemic, regional, and intratumoral leukocyte activation (Hamlin 1968;Kreider et al 1984). During tumor progression, tumors adopt immunosuppressive strategies, such as downregulation of HLA class I molecules (Lassam and Jay 1989) and secretion of anti-inflammatory cytokines such as TGF-␤ (Daughaday and Deuel 1991;Hazelbag et al 2002), leading to further tolerization of natural antitumor responses.…”