The present invention relates to methods for modulating immune response based on binding I-domain of CD11b on the tumor associated myeloid cells (TAMCs) in the tumor microenvironment. Particularly, binding to I-domain of CD11b with anti-CD11b-I-domain antibody triggers immunostimulatory environment that have one or more of the following effects in the tumor microenvironment: increase the inflammatory cytokine in the tumor microenvironment, decrease the population of IDO+ myeloid suppresser cells, up-regulate M1 marker over M2 marker on the tumor associated macrophage, increase M1:M2 tumor associated macrophage ratio, promote differentiation of dendritic cells (DC), nature killer dendritic cells (NKDC), and plasmacytoid dendritic cells (pDC), increase population of 4-1BB+PD-1+ neoantigen specific CD8 T cells. Converting cold (non-inflamed) to hot (inflamed) tumor by binding to I-domain of CD11b with anti-CD11b-I-domain antibody allows enhanced effectiveness of immune response modulator.
