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Abstract: Within the European Fusion Technology Programme, the Helium-Cooled Lithium Lead (HCLL) breeding blanket concept is one of the two EU lines to be developed for a Long Term fusion reactor, in particular with the aim of manufacturing a Test Blanket Module (TBM) to be implemented in ITER. The HCLL-TBM is foreseen to be located in an ITER equatorial port, being housed inside a steel-supporting frame, actively cooled by pressurized water. That supporting frame has been designed to house two different TBMs, providing two cavities separated by a dividing Plate 20cm thick. As the nuclear response of HCLL-TBM might vary accordingly to the supporting frame configuration and composition, at the Department of Nuclear Engineering of the University of Palermo, a parametric study has been launched to investigate such an influence. Previous works dealt with the dependence of the nuclear response of HCLL-TBM on the configuration of a homogeneous frame, the present one has been focused on the investigation of the potential influence of coolant distribution within the frame on the radiation-induced damage of the HCLL-TBM structural material. To this purpose, a detailed parametric study of the HCLL-TBM nuclear response has been performed by means of 3D-Monte Carlo neutronic analyses to asses both the rates of displacements per atom and helium and hydrogen production within the structural material. A semi-heterogeneous model of the supporting frame, assuming a realistic coolant distribution, and a 3D heterogeneous model of the HCLL-TBM, taking into account EUROFER as structural material, has been set-up. Therefore, the models of the TBM and of its frame have been inserted into the existing 3D ITER one, simulating realistically the reactor lay-out up to the cryostat and providing for a proper D-T neutron source. The analyses have been performed by means of the MCNP-4C code, and the results obtained are reported and critically discussed. [Copyright &y& Elsevier]