Host Defense and Survival in Lung Cancer
Host Defense and Survival in Lung Cancer
abstract & commentary
Synopsis: Certain pathologic changes associated with a host immune response correlate with survival in lung cancer patients. Lymphocytic infiltration of the primary tumor and a cellular response in the regional nodes will predict outcome.
Source: Di Giorgio A, et al. Cancer 2000;89:2038-2045.
If you believe that adjuvant therapy in lung cancer has potential benefits, how do you select eligible patients? Most oncologists consider factors such as the patient’s age and the tumor’s stage and grade. Although no method of selecting patients has emerged for which adjuvant therapy has proven to be effective, the retrospective analysis by Di Giorgio and associates looks at unique risk factors that might ultimately better define which patients are at high risk for recurrence.
The study by Di Giorgio et al was designed to evaluate whether the pathologic detection of an anticancer immune response in lung cancer specimens correlated with the clinical outcome. One hundred seventy-two patients with resectable lung cancer who survived beyond the postoperative period were selected from more than 3000 cases of lung carcinoma treated at the University of Rome from 1960 to 1997. Slides from at least eight lymph nodes were required for each eligible patient.
From these 172 patients, Di Giorgio et al retrieved the slides of 2064 lymph nodes (mean 12, range 8-27). These regional lymph nodes were assessed for sinus histiocytosis (SH), paracortical lymphoid cell hyperplasia (PLCH) or follicular hyperplasia of the cortical area (FHCA). Sinus histiocytosis and PLCH were considered to be indicators of an antitumor cell-mediated immune response, whereas FHCA was considered to be evidence for an antibody-mediated response. The primary tumors were also assessed for lymphocytic infiltration, a surrogate marker of a local immune response.
Using methods described in the paper, patients were divided into four "immunomorphologic" groups: predominantly cellular immune response (20%), predominantly humoral immune response (11%), both cellular and humoral response (34%), and no evident immune response (35%). These subtypes showed no statistical correlation with gender, stage, or cell type. Of interest, however, was the relationship between survival and the immune response category.
Patients with a strong cellular immune response in the lymph nodes had the highest 10-year survival rate (about 60%), whereas those with a humoral response or no immune response at all had the worst 10-year survival (< 5%). An intermediate survival curve was seen for patients with both a cellular and humoral immune response (about 25%). A marked degree of lymphocytic infiltration in the primary tumor (rather than the lymph nodes) was also associated with an improved survival. In fact, a Cox regression analysis, which included the stage and histologic subtype, identified only lymphocytic infiltration of the primary tumor and the "immunomorphologic" pattern of the locoregional nodes as the most reliable independent variables for predicting survival after curative surgery for lung cancer.
COMMENT by Kenneth W. Kotz, MD
Using predefined patterns of an immune response, Di Giorgio et al found evidence of an active host defense in the regional lymph nodes in 64.5% of patients and in the primary tumor in 36.6% of patients. Older patients tended to have less immunoreactivity, but this did not reach statistical significance. The patients with small cell lung cancer tended to have less immunoreactivity than patients with non-small cell lung cancer, but for those patients who did react, the proportion of cellular and humoral responses was the same.
The most striking finding is the relationship between survival and the type of immune response in the regional nodes. To repeat, the highest survival was for patients with a cellular response. The addition of a humoral response worsened survival, and a humoral response alone was as bad as no response at all. Di Giorgio et al hypothesize that a cellular response prevents lymph node metastases, whereas a humoral response facilitates lymph node metastases. For example, the nodes of most node-negative tumors contained a predominantly cellular response whereas the nodes of most node-positive tumors contained mostly a humoral response.
The exact mechanism behind these observations is unknown. Di Giorgio et al suggest that a humoral response (perhaps due to increasing tumor size and shedding of antigens) might block the cytotoxic action of T-cells. Obviously, the biology of metastasizing cancer cells is extremely complicated. However, it is hoped that retrospective analyses such as the one by Di Giorgio et al might eventually lead to better selection of high-risk lung cancer patients so that any benefit afforded by adjuvant therapy can be more easily demonstrated.
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