Cancer immunology--analysis of host and tumor factors for personalized medicine

Abstract

Immune cells in the tumor microenvironment have an important role in regulating tumor progression. Therefore, stimulating immune reactions to tumors can be an attractive therapeutic and prevention strategy. Cancer cells and host cells constantly interact with each other in the tumor microenvironment; thus, cancer immunology is an interdisciplinary area where integrated analysis of both host and tumor factors is needed. Cancer represents a heterogeneous group of diseases with different genetic and epigenetic alterations; therefore, molecular classification of cancer (for example lung, prostate and breast cancers) is an important component in clinical decision making. However, most studies on antitumor immunity and clinical outcome lack analysis of tumor molecular biomarkers. In this Review, we discuss colorectal cancer as a prototypical example of cancer. Common molecular classifiers of colon cancer include KRAS, BRAF and PIK3CA mutations, microsatellite instability, LINE-1 methylation, and CpG island methylator phenotype. Since tumor molecular features and immune reactions are inter-related, a comprehensive assessment of these factors is critical. Examining the effects of tumor-host interactions on clinical outcome and prognosis represents an evolving interdisciplinary field of molecular pathological epidemiology. Pathological immunity evaluation may provide information on prognosis and help identify patients who are more likely to benefit from immunotherapy.

Figure 1

Various immune-cell reaction patterns can be observed upon pathologic examination of a cancer biopsy. The level of immune-cell infiltration varies widely between tumors (from absent to intense); tumors with considerable immune reactions are depicted. a | Lymphocytic infiltrates in tumor stroma (arrowheads) between glandular structures formed by neoplastic cells, as well as on top of neoplastic cells (arrows) as a form of tumor-infiltrating lymphocytes (magnification, ×100). b | Tumor-infiltrating lymphocytes from part a (arrows) are shown in a high-power view (magnification, ×400). c | Immune reactions surround the tumor as a form of peritumoral lymphocytic reaction (empty arrowhead), and are observed in smooth muscle and adipose tissue (empty arrows) with some distance from tumor (magnification, ×40).

Figure 2

Putative inter-relationship between tumor molecular changes, host immune response, regional lymph nodes, disease stage and prognosis in colorectal cancer. Tumor molecular changes are associated with both the host immune response and with patient prognosis.^,, The host immune response is associated with early-stage disease and an increased number of lymph nodes detected in resection specimens. Immune reaction may promote proliferation of lymphocytes and enlargement of regional lymph nodes, potentially facilitating lymph-node dissection in gross pathology examination and increasing in the number of recovered lymph nodes. The lymph-node count is associated with good prognosis, independent of the host immune response, tumor stage and tumor molecular variables. Thus, a comprehensive assessment of host immune response, disease staging, node count, and tumor molecular variables is necessary to evaluate the clinical utility of host immune response evaluation.