By comparing the anti-tumor efficacy of anti-CTLA-4 antibody in mice maintained under conditions in specific-pathogen-free (SPF) that are free of particular pathogens, and germ-free (GF) that harbor no living microorganisms, a pioneering study found that anti-CTLA-4 antibody treatment controlled tumor progression in SPF but not in GF animals [24]. Here, CTLA4 is linked to neoplasm.