**3.1 Tumor infiltrating lymphocytes (TILs)**

Under the immune surveillance, lymphocytes differentiate between self and non-self-cells and antigens. Any self-cell when gets transformed and starts proliferating as cancer, lymphocytes infiltrate into that site, recognize abnormally growing cells and activate themselves to remove these *not so self*, cancerous cells. These lymphocytes are named as Tumor Infiltrating Lymphocytes (TILs). It so happens sometimes that these TILs fail to perform their function efficiently which may lead to cancer progression. In such cases, it was found that the TILs are not enough in number to show effective cytotoxicity, though have ability to specifically recognize tumor cells, stop their growth and eventually kill them. Thus, to develop any cellular therapy, the first and the foremost approach was to expand TILs, which have infiltrated into the tumor site with anti-tumor potential. These cells can be isolated from cancer origin tissue by resection and expanded *ex-vivo* to a sufficient number to improve their anti-tumor activity. These are then infused back into the patient as ACT therapy (**Figure 3a**). The TILs used in the therapy are autologous lymphocytes as these are derived from the tumor site.

Hence, for the development of ACT, antitumor lymphocytes are grown *in-vitro* up to a number of 1011–1012, followed by a process of selection of specific tumor recognizing cells with effector functions. These cells when infused in the patient, behave like live drug, which proliferate when encounter tumor antigen in the host and help in tumor regression. Though the process of cellular expansion *in-vitro* does not absolutely match with *in-vivo* environment around the tumor, which has certain immune inhibitory responses. Thus, in ACT, a favorable tumor microenvironment is necessary prior to the therapy which should support the anti-tumor immune function of the infused TILs [37].
