REGIONAL IMMUNOSUPPRESSION IN ESOPHAGEAL SQUAMOUS CANCER - EVIDENCE FROM FUNCTIONAL-STUDIES WITH MATCHED LYMPH-NODES

Although production of immunosuppressive factor(s) by esophageal squam ous cancer has been demonstrated, systemic immunosuppression occurs la te, Whether local immunosuppression by tumor-derived factors occurs in vivo as a potential mechanism of escape from immune surveillance is u nknown, We found that lymphocytes from nodes draining distal esophagea l squamous tumors in 23 consecutive patients had depressed proliferati ve and cytotoxic responsiveness relative to both lymphocytes from a re ference node outside the field of drainage and matched PBL from the sa me patient. In a subset of patients in which more than one tumor-drain ing node was examined, a radial or zonal immunosuppression relative to the primary tumor was evident. The findings were unrelated to surgery or anatomic location because all but 2 of 26 control patients with es ophagogastric adenocarcinoma had normal or enhanced lymphocyte respons iveness in the tumor-draining node, The absence of overt or even micro metastatic nodal disease, as determined by immunostaining for cytokera tin expression, coupled with the long-term survival of several of the patients, strongly suggests that the immunosuppressive effect is due t o mechanisms other than metastases, and may be a premetastatic occurre nce, We conclude that regional immunesuppression does exist in patient s with esophageal squamous cancer when systemic immunity is still well preserved, The local immune suppression inhibits the generation of ly mphokine-activated killer (LAK) cells and may be an impediment to pote ntial immunotherapeutic strategies.