Question

According to a study performed over a -year time period and reported in the Annals of Surgery, 151 patients with malignant melanoma were treated with BCG immunotherapy (NB. BCG is a weakened but live strain of Mycobacterium bovis used as part of the "childhood vaccination regime in European countries", but not in the US.) alone or as an adjunct to surgical therapy. One finding in these studies was that direct injection of metastatic melanoma lesions limited to the skin resulted in 90% regression of the injected lesions and 17% regression of uninjected lesions in immunocompetent patients. Approximately 25% of these patients remained free of disease for 1 to 6 years. Contrastingly, however, direct injections of BCG into the melanomic nodules of patients with subcutaneous metastases resulted in a lower incidence of local control and no long-term survivors.

Give what you know about the immune system, to date, and specifically in respect to the Type IV DTH, how would you interpret these clinical results in terms of the immune mechanism(s) and the differences observed in the two test groups?

Answer 1

According to the information, there are two test groups of patients. One groups which is having lesions limited to skin is injected with BCG and shows protection against myeloma. Other groups having subcutaneous lesions under skin when injected with BCG shows no protection against myeloma. Here, two points must be taken into account.

Firstly, the first group is having only a limited spread of cancerous cells whereas the second group has metastatic myeloma. This means that the first group is more susceptible to anti-cancerous therapies as compared to the second group. Secondarily, the first groups has limited spread of myeloma suggesting that the subcutaneous tissue including the lymphatic system is devoid of any cancerous cells. This makes it easier to be attached by anti-cancerous therapeutics and a reversion would not be obtained from the body.

Here, the reversion would be generally followed by onset of either sudden hypersensitivity or delayed-type hypersensitivity or DTH. Since cancerous cells are not considered as foreign by the body, they generally show DTH in response to a therapeutic agent. Here, subsequent injection with BCG would provide a DTH response since the cancercell surrounding healthy tissue would secrete appropriate interleukins in response to the therapeutic and hence it would help in destruction of the cancerous cell. In this way, BCG would utilize the DTH response in favour of the body and prevent/slow down the growth of cancerous cells in the body.